Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines
Identifieur interne : 000E33 ( Ncbi/Merge ); précédent : 000E32; suivant : 000E34Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines
Auteurs : Lara Šoši ; P L Kristian Selbo ; Zuzanna K. Kotkowska ; Thomas M. Kündig ; Anders H Gset ; P L JohansenSource :
- Cancers [ 2072-6694 ] ; 2020.
Abstract
Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS2a combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.
Url:
DOI: 10.3390/cancers12010165
PubMed: 31936595
PubMed Central: 7016662
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PMC:7016662Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines</title><author><name sortKey="Sosi, Lara" sort="Sosi, Lara" uniqKey="Sosi L" first="Lara" last="Šoši">Lara Šoši</name><affiliation><nlm:aff id="af1-cancers-12-00165">Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</nlm:aff></affiliation></author><author><name sortKey="Selbo, P L Kristian" sort="Selbo, P L Kristian" uniqKey="Selbo P" first="P L Kristian" last="Selbo">P L Kristian Selbo</name><affiliation><nlm:aff id="af2-cancers-12-00165">Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Ullernchausséen 70, 0379 Oslo, Norway;<email>selbo@rr-research.no</email></nlm:aff></affiliation></author><author><name sortKey="Kotkowska, Zuzanna K" sort="Kotkowska, Zuzanna K" uniqKey="Kotkowska Z" first="Zuzanna K." last="Kotkowska">Zuzanna K. Kotkowska</name><affiliation><nlm:aff id="af1-cancers-12-00165">Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</nlm:aff></affiliation></author><author><name sortKey="Kundig, Thomas M" sort="Kundig, Thomas M" uniqKey="Kundig T" first="Thomas M." last="Kündig">Thomas M. Kündig</name><affiliation><nlm:aff id="af1-cancers-12-00165">Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</nlm:aff></affiliation></author><author><name sortKey="H Gset, Anders" sort="H Gset, Anders" uniqKey="H Gset A" first="Anders" last="H Gset">Anders H Gset</name><affiliation><nlm:aff id="af3-cancers-12-00165">PCI Biotech AS, Ullernchausséen 64, 0379 Oslo, Norway;<email>Anders.Hogset@pcibiotech.no</email></nlm:aff></affiliation></author><author><name sortKey="Johansen, P L" sort="Johansen, P L" uniqKey="Johansen P" first="P L" last="Johansen">P L Johansen</name><affiliation><nlm:aff id="af1-cancers-12-00165">Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31936595</idno><idno type="pmc">7016662</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016662</idno><idno type="RBID">PMC:7016662</idno><idno type="doi">10.3390/cancers12010165</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000912</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000912</idno><idno type="wicri:Area/Pmc/Curation">000912</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000912</idno><idno type="wicri:Area/Pmc/Checkpoint">000071</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000071</idno><idno type="wicri:Area/Ncbi/Merge">000E33</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines</title><author><name sortKey="Sosi, Lara" sort="Sosi, Lara" uniqKey="Sosi L" first="Lara" last="Šoši">Lara Šoši</name><affiliation><nlm:aff id="af1-cancers-12-00165">Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</nlm:aff></affiliation></author><author><name sortKey="Selbo, P L Kristian" sort="Selbo, P L Kristian" uniqKey="Selbo P" first="P L Kristian" last="Selbo">P L Kristian Selbo</name><affiliation><nlm:aff id="af2-cancers-12-00165">Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Ullernchausséen 70, 0379 Oslo, Norway;<email>selbo@rr-research.no</email></nlm:aff></affiliation></author><author><name sortKey="Kotkowska, Zuzanna K" sort="Kotkowska, Zuzanna K" uniqKey="Kotkowska Z" first="Zuzanna K." last="Kotkowska">Zuzanna K. Kotkowska</name><affiliation><nlm:aff id="af1-cancers-12-00165">Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</nlm:aff></affiliation></author><author><name sortKey="Kundig, Thomas M" sort="Kundig, Thomas M" uniqKey="Kundig T" first="Thomas M." last="Kündig">Thomas M. Kündig</name><affiliation><nlm:aff id="af1-cancers-12-00165">Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</nlm:aff></affiliation></author><author><name sortKey="H Gset, Anders" sort="H Gset, Anders" uniqKey="H Gset A" first="Anders" last="H Gset">Anders H Gset</name><affiliation><nlm:aff id="af3-cancers-12-00165">PCI Biotech AS, Ullernchausséen 64, 0379 Oslo, Norway;<email>Anders.Hogset@pcibiotech.no</email></nlm:aff></affiliation></author><author><name sortKey="Johansen, P L" sort="Johansen, P L" uniqKey="Johansen P" first="P L" last="Johansen">P L Johansen</name><affiliation><nlm:aff id="af1-cancers-12-00165">Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</nlm:aff></affiliation></author></analytic><series><title level="j">Cancers</title><idno type="eISSN">2072-6694</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS<sub>2a</sub>). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS<sub>2a</sub> combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Osipov, A" uniqKey="Osipov A">A. Osipov</name></author><author><name sortKey="Murphy, A" uniqKey="Murphy A">A. Murphy</name></author><author><name sortKey="Zheng, L" uniqKey="Zheng L">L. Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzone, L" uniqKey="Falzone L">L. Falzone</name></author><author><name sortKey="Salomone, S" uniqKey="Salomone S">S. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cancers (Basel)</journal-id><journal-id journal-id-type="iso-abbrev">Cancers (Basel)</journal-id><journal-id journal-id-type="publisher-id">cancers</journal-id><journal-title-group><journal-title>Cancers</journal-title></journal-title-group><issn pub-type="epub">2072-6694</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31936595</article-id><article-id pub-id-type="pmc">7016662</article-id><article-id pub-id-type="doi">10.3390/cancers12010165</article-id><article-id pub-id-type="publisher-id">cancers-12-00165</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Šošić</surname><given-names>Lara</given-names></name><xref ref-type="aff" rid="af1-cancers-12-00165">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-5310-057X</contrib-id><name><surname>Selbo</surname><given-names>Pål Kristian</given-names></name><xref ref-type="aff" rid="af2-cancers-12-00165">2</xref></contrib><contrib contrib-type="author"><name><surname>Kotkowska</surname><given-names>Zuzanna K.</given-names></name><xref ref-type="aff" rid="af1-cancers-12-00165">1</xref></contrib><contrib contrib-type="author"><name><surname>Kündig</surname><given-names>Thomas M.</given-names></name><xref ref-type="aff" rid="af1-cancers-12-00165">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-2562-9951</contrib-id><name><surname>Høgset</surname><given-names>Anders</given-names></name><xref ref-type="aff" rid="af3-cancers-12-00165">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-5055-6299</contrib-id><name><surname>Johansen</surname><given-names>Pål</given-names></name><xref ref-type="aff" rid="af1-cancers-12-00165">1</xref><xref rid="c1-cancers-12-00165" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-cancers-12-00165"><label>1</label>Department of Dermatology, University Hospital Zurich & University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;<email>lara.sosic@usz.ch</email> (L.Š.);<email>zuzanna.kotkowska@usz.ch</email> (Z.K.K.);<email>thomas.kuendig@usz.ch</email> (T.M.K.)</aff><aff id="af2-cancers-12-00165"><label>2</label>Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Ullernchausséen 70, 0379 Oslo, Norway;<email>selbo@rr-research.no</email></aff><aff id="af3-cancers-12-00165"><label>3</label>PCI Biotech AS, Ullernchausséen 64, 0379 Oslo, Norway;<email>Anders.Hogset@pcibiotech.no</email></aff><author-notes><corresp id="c1-cancers-12-00165"><label>*</label>Correspondence: <email>pal.johansen@usz.ch</email>; Tel.: +41-44-255-8616</corresp></author-notes><pub-date pub-type="epub"><day>09</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>1</month><year>2020</year></pub-date><volume>12</volume><issue>1</issue><elocation-id>165</elocation-id><history><date date-type="received"><day>16</day><month>12</month><year>2019</year></date><date date-type="accepted"><day>07</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 by the authors.</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS<sub>2a</sub>). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS<sub>2a</sub> combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.</p></abstract><kwd-group><kwd>photochemical internalization</kwd><kwd>photodynamic therapy</kwd><kwd>cytosolic delivery</kwd><kwd>cancer vaccination</kwd><kwd>cancer immunotherapy</kwd><kwd>cross-presentation</kwd><kwd>CTL</kwd></kwd-group></article-meta></front><floats-group><fig id="cancers-12-00165-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Photochemical internalization. The drug is co-administered with the photosensitizer. The photosensitizer accumulates in cell membranes and the drug is taken up through endocytosis. ROS are generated during illumination, which leads to disruption of the endocytic membrane and release of the drug into the cytosol (modified with courtesy from PCI Biotech: <uri xlink:href="http://pcibiotech.no/what-is-pci/">http://pcibiotech.no/what-is-pci/</uri>).</p></caption><graphic xlink:href="cancers-12-00165-g001"></graphic></fig><fig id="cancers-12-00165-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Antigen uptake, processing, and T-cell presentation in PCI-based vaccination. Photosensitizer and antigen are endocytosed into an antigen-presenting cell (APC). The photosensitizer is attached to the endosomal membrane and the antigen is contained in the endosomal lumen. After a wash-out period, where excess photosensitizer dissociates from the outer plasma membrane, light exposure causes endosomal eruption and cytosolic release of antigen for proteasomal degradation and MHC class-I presentation to CD8 T cells. In the absence of the photosensitizer and light, endosomes mature and fuse with lysosomes for MHC class-II presentation of digested antigens to CD4 T cells.</p></caption><graphic xlink:href="cancers-12-00165-g002"></graphic></fig><fig id="cancers-12-00165-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>PRISMA flow diagram for systematic selection and review of studies.</p></caption><graphic xlink:href="cancers-12-00165-g003"></graphic></fig><table-wrap id="cancers-12-00165-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">cancers-12-00165-t001_Table 1</object-id><label>Table 1</label><caption><p>Photosensitizers approved or under clinical trials.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Name</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Ex Wave-Length (nm)</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Manufacturer</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Application</th></tr></thead><tbody><tr><td colspan="4" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>FIRST GENERATION PHOTOSENSITIZERS</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Porfimer sodium</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">630</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Axcan Pharma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of esophageal cancer, lung adenocarcinoma, and endobronchial cancer</td></tr><tr><td colspan="4" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>SECOND GENERATION PHOTOSENSITIZERS/Prodrugs</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5-aminolaevulinic acid</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">635</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">DUSA<break></break>Stabiopharma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of mild to moderate actinic keratosis Fluorescence guided resection of glioma</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Methyl-aminolevulinic acid</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">579–670</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Galderma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of non-hyperkeratotic actinic keratosis and basal cell carcinoma</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Temoporfin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">652</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Biolitec</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of advanced head and neck cancer</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Talaporfin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">664</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Meiji Seika<break></break>Novartis</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of early centrally located lung cancer</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Verteporfin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">690</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Novartis</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of age-related macular degeneration</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Redaporfin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">749</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Luzitin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of biliary tract cancer</td></tr><tr><td colspan="4" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>PHOTOSENSITIZERS UNDER CLINICAL INVESTIGATIONS</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fotolon</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">665</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Apocare Pharma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of nasopharyngeal, sarcoma</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hexylaminolevulinate</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">635</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Photocure</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of HPV-induced cervical precancerous lesions and non-muscle invasive bladder cancer</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Radachlorin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">662</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rada-pharma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of skin cancer</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Photochlor (HTTP)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">664</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rosewell Park</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of head and neck cancer</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Padeliporfin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">762</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Negma-Lerads</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of prostate cancer</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Motexafin lutetium</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">732</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pharmacyclics</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of coronary artery disease</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rostaprofin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">664</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Miravant</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of age-related macular degeneration</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Talaporfin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">664</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Meiji Seika</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDT of colorectal neoplasms, liver metastasis</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fimaporfin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">435</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI Biotech</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI of cutaneous or sub-cutaneous malignancies, cholangiocarcinoma and PCI of vaccine antigens</td></tr></tbody></table></table-wrap><table-wrap id="cancers-12-00165-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">cancers-12-00165-t002_Table 2</object-id><label>Table 2</label><caption><p>Articles on PCI of cytotoxic therapeutics reviewed in this paper.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author, Year, Country</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Tested Tissue/Cells</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">PCI-Internalized Molecule and Photosensitizer</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Model</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Primary Outcome</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Reference</th></tr></thead><tbody><tr><td colspan="6" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>PRECLINICAL STUDIES</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Olsen et al., 2013</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dox-resistant human sarcoma cell line MES-SA/Dx5 and non-resistant MES-SA line</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">rGel and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Cell culture</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI circumvents the mechanisms of PDT resistance in dox-resistant human sarcoma cell lines </td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B25-cancers-12-00165" ref-type="bibr">25</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">O’Rourke et al., 2017</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rat cortical mixed glial cells, DRG, and satellite glia, HNSCC cell line</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bleomycin and TPPS<sub>2a</sub> or TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Cell culture</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">DRG neurons can survive TPCS<sub>2a</sub> and TPPS<sub>2a</sub>-mediated PCI at doses enough to kill the carcinoma cell line</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B26-cancers-12-00165" ref-type="bibr">26</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Martínez-Jothar et al., 2019</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Human HER2+ and HER2− breast<break></break>cancer cell lines</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Saporin or placebo in PEGylated NP and TPPS<sub>2a</sub>, functionalized with 11A4 nanobody</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Cell culture</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI of saporin-loaded PEGylated NP can be used to selectively induce cell death of HER2+ breast cancer cells</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B27-cancers-12-00165" ref-type="bibr">27</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Norum et al., 2017</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Murine CC and murine MGC cells in athymic and thymic BALB/c mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bleomycin and AlPcS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vivo: Murine allograft model</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI of bleomycin had a curative effect on tumor cells in thymic, but not in athymic mice and induced immune responses sufficient to reject new tumor cells for up to two months</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B28-cancers-12-00165" ref-type="bibr">28</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Stratford et al., 2013</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Human sarcoma cell line and human fibrosarcoma cell line, human sarcoma cells in athymic nude mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CD133-targeting immunotoxins and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Cell culture<break></break>In vivo: Murine xenograft model</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Proof-of-concept: PCI of CD133-targeting immunotoxins reduces cellular viability and proliferative capacity of sarcoma cells and inhibits tumor grafting</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B29-cancers-12-00165" ref-type="bibr">29</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bostad et al., 2015</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Human CA, ALL, malignant melanoma, and TNBC (CD133+ and CD133−) cell lines, human CA cells in athymic nude mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CD133-targeting immunotoxin and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Cell culture<break></break>In vivo: Murine xenograft model</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Efficient PCI of CD133-targeting immunotoxins in human cancer cell lines in vitro.<break></break>Proof-of-concept: Anti-tumor response after PCI of CD133-targeting immunotoxins in vivo</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B30-cancers-12-00165" ref-type="bibr">30</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Eng et al., 2018</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Human TNBC, amelanotic human melanoma, human Melmet cell lines, amelanotic human melanoma cells in athymic nude mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CSPG4-targeting toxin and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Cell culture<break></break>In vivo: Murine xenograft model</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI of CSPG4-based immunotoxins induces death of CSPG4-positive and drug-resistant cells of TNBC and malignant melanoma origin, in vitro and in vivo</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B32-cancers-12-00165" ref-type="bibr">32</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Berstad et al., 2015</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Head and neck squamous cell carcinoma cell line. A-431or SCC-026 cells in athymic nude mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">rGel/EGF (an EGFR-targeted fusion protein)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Cell culture<break></break>In vivo: Murine xenograft model</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI increased the cytotoxicity of rGel/EGF in EGFR-expressing cells. PCI of rGel/EGF induced significant antitumor effects in A-431 xenograft mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B31-cancers-12-00165" ref-type="bibr">31</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Weyergang et al., 2018</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEGFR2-expressing endothelial cells, murine colon carcinoma, and breast carcinoma cell lines in vitro and in BALB/c and athymic nude mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEGF<sub>121</sub>/rGel and TPPS<sub>2a</sub> (in vitro) or TPCS<sub>2a</sub> (in vivo)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Cell culture<break></break>In vivo: Murine allograft model</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI of VEGF<sub>121</sub>/rGel directly targets tumor cells and induces T-cell mediated tumor remission, reduced perfusion, and produced tumor protection in vivo</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B63-cancers-12-00165" ref-type="bibr">63</xref>]</td></tr><tr><td colspan="6" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>CLINICAL TRIALS IN HUMAN</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sultan et al., 2016, England</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Patients (18 to 85 years) with local recurrent, advanced, or metastatic cutaneous or subcutaneous malignancies</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bleomycin and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Phase I,<break></break>First-in-human</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Administration of TPCS<sub>2a</sub> was found to be safe and tolerable by all patients. No significant systemic adverse events related to photochemical internalization treatment occurred.</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B52-cancers-12-00165" ref-type="bibr">52</xref>,<xref rid="B64-cancers-12-00165" ref-type="bibr">64</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Jerjes et al., 2019, England</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">57-year-old male with end-stage recurrent and therapy-resistant chondroblastic osteosarcoma in the right mandible</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bleomycin and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Case report</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Illuminated areas responded favorably to treatment. PCI anti-tumor activity was superior to PDT, clinically and histopathologically. Peri-illumination pain</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B65-cancers-12-00165" ref-type="bibr">65</xref>]</td></tr></tbody></table><table-wrap-foot><fn><p>Dox: Doxorubicine. DRG: dorsal root ganglion neurons. HNSCC: head and neck squamous cell carcinoma. NP: Nanoparticles. CC: Colon carcinoma. MGC: Mammary gland carcinoma. CA: Colorectal adenocarcinoma. ALL: Acute lymphocytic leukemia. TNBC: Triple negative breast cancer. CSPG4: cell surface chondroitin sulfate proteoglycan 4. rGel: recombinant Gelonin. EGFR: epidermal growth factor receptor.</p></fn></table-wrap-foot></table-wrap><table-wrap id="cancers-12-00165-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">cancers-12-00165-t003_Table 3</object-id><label>Table 3</label><caption><p>Articles on PCI in immunotherapy reviewed in this paper.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author, Year, Country</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">PCI-Internalized Molecule and Photosensitizer</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Model</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Primary Outcome</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Reference</th></tr></thead><tbody><tr><td colspan="5" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>PCI IN IMMUNOTHERAPY, preclinical studies</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Waeckerle-Men et al., 2013</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">OVA and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: DCs<break></break>In vivo: Autologously immunized C57BL/6 mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Proof-of-concept: Feasibility of PCI of OVA in DCs for stimulation of CTL responses in vitro.<break></break>Autologous vaccination of mice with PCI-treated DCs led to improved MHC class-I-restricted and antigen-specific CTL response</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B33-cancers-12-00165" ref-type="bibr">33</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Håkerud et al., 2014</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">OVA and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: DCs<break></break>In vivo: Allograft model, B16-OVA-melanoma cells in C57BL/6 mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Proof-of-concept: Photosensitization and immunization directly in vivo.<break></break>PCI-vaccination stimulated antigen-specific CD8 memory cells and prevented tumor growth</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B34-cancers-12-00165" ref-type="bibr">34</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Håkerud et al., 2015</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">OVA and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: DCs<break></break>In vivo: Allograft model, B16-OVA-melanoma cells in C57BL/6 mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prophylactic PCI-based vaccination prevented tumor grafting and therapeutic vaccination reduced tumor growth and improved mouse survival</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B35-cancers-12-00165" ref-type="bibr">35</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hjálmsdóttir et al., 2016</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">DPPC Liposomes loaded with OVA or TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: TPCS<sub>2a</sub>-and OVA-loaded liposomes<break></break>Ex vivo CTL in blood and spleen of C57BL/6 mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Liposomes can be used for PCI-based cytosolic antigen targeting and CTL cross priming and may protect photosensitizers from light-induced inactivation</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B20-cancers-12-00165" ref-type="bibr">20</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bruno et al., 2015</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PLGA microparticles loaded with OVA and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vivo: Allograft model, B16-OVA-melanoma cells in C57BL/6 mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The combination of PLGA microparticle–based antigen delivery and photosensitization induces stimulation of antigen-specific CTL in a mouse model</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B22-cancers-12-00165" ref-type="bibr">22</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Haug et al.</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: OVA and TPCS<sub>2a.</sub> In vivo: HPV 16 E7 protein (HPV43–78) and from tyrosinase-related protein 2 (TRP2 180–188) and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vitro: Macrophages<break></break>In vivo: C57BL/6 mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI promotes delivery of peptide antigens to the cytosol of APCs in vitro. Successful induction of antigen-specific CTL responses following intradermal peptide vaccination using PCI in vivo</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B36-cancers-12-00165" ref-type="bibr">36</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Varypataki et al., 2019</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">OVA and TPCS<sub>2a</sub> or lethally irradiated B16-OVA and TPCS<sub>2a</sub></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In vivo: Allograft model, B16-OVA-melanoma cells in C57BL/6, congenic CD45.1, MHC class II- and CD40L-deficient mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PCI-based vaccination caused tumor regression independent of MHC class II or CD4 T cells in melanoma-bearing mice</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B37-cancers-12-00165" ref-type="bibr">37</xref>]</td></tr></tbody></table><table-wrap-foot><fn><p>OVA: Chicken ovalbumin. DCs: Dendritic cells. DPPC: Dipalmitoyl phosphatidylcholine. PLGA: poly(lactide-co-glycolide).</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list></list><tree><noCountry><name sortKey="H Gset, Anders" sort="H Gset, Anders" uniqKey="H Gset A" first="Anders" last="H Gset">Anders H Gset</name><name sortKey="Johansen, P L" sort="Johansen, P L" uniqKey="Johansen P" first="P L" last="Johansen">P L Johansen</name><name sortKey="Kotkowska, Zuzanna K" sort="Kotkowska, Zuzanna K" uniqKey="Kotkowska Z" first="Zuzanna K." last="Kotkowska">Zuzanna K. Kotkowska</name><name sortKey="Kundig, Thomas M" sort="Kundig, Thomas M" uniqKey="Kundig T" first="Thomas M." last="Kündig">Thomas M. Kündig</name><name sortKey="Selbo, P L Kristian" sort="Selbo, P L Kristian" uniqKey="Selbo P" first="P L Kristian" last="Selbo">P L Kristian Selbo</name><name sortKey="Sosi, Lara" sort="Sosi, Lara" uniqKey="Sosi L" first="Lara" last="Šoši">Lara Šoši</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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