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Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Identifieur interne : 001102 ( Pmc/Curation ); précédent : 001101; suivant : 001103

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Auteurs : Daniel Sur ; Andrei Havasi ; Calin Cainap ; Gabriel Samasca ; Claudia Burz ; Ovidiu Balacescu [Roumanie] ; Iulia Lupan [Roumanie] ; Diana Deleanu ; Alexandru Irimie [Roumanie]

Source :

RBID : PMC:7019711

Abstract

Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient’s T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient’s body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.


Url:
DOI: 10.3390/jcm9010182
PubMed: 31936611
PubMed Central: 7019711

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PMC:7019711

Le document en format XML

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<p>Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient’s T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient’s body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.</p>
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</author>
<author>
<name sortKey="Miyamoto, M" uniqKey="Miyamoto M">M. Miyamoto</name>
</author>
<author>
<name sortKey="Kondo, S" uniqKey="Kondo S">S. Kondo</name>
</author>
<author>
<name sortKey="Nishimura, T" uniqKey="Nishimura T">T. Nishimura</name>
</author>
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</TEI>
<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">J Clin Med</journal-id>
<journal-id journal-id-type="iso-abbrev">J Clin Med</journal-id>
<journal-id journal-id-type="publisher-id">jcm</journal-id>
<journal-title-group>
<journal-title>Journal of Clinical Medicine</journal-title>
</journal-title-group>
<issn pub-type="epub">2077-0383</issn>
<publisher>
<publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">31936611</article-id>
<article-id pub-id-type="pmc">7019711</article-id>
<article-id pub-id-type="doi">10.3390/jcm9010182</article-id>
<article-id pub-id-type="publisher-id">jcm-09-00182</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-0926-4614</contrib-id>
<name>
<surname>Sur</surname>
<given-names>Daniel</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-09-00182">1</xref>
<xref ref-type="aff" rid="af2-jcm-09-00182">2</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Havasi</surname>
<given-names>Andrei</given-names>
</name>
<xref ref-type="aff" rid="af2-jcm-09-00182">2</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cainap</surname>
<given-names>Calin</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-09-00182">1</xref>
<xref ref-type="aff" rid="af2-jcm-09-00182">2</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-7645-0716</contrib-id>
<name>
<surname>Samasca</surname>
<given-names>Gabriel</given-names>
</name>
<xref ref-type="aff" rid="af3-jcm-09-00182">3</xref>
<xref rid="c1-jcm-09-00182" ref-type="corresp">*</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Burz</surname>
<given-names>Claudia</given-names>
</name>
<xref ref-type="aff" rid="af2-jcm-09-00182">2</xref>
<xref ref-type="aff" rid="af3-jcm-09-00182">3</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Balacescu</surname>
<given-names>Ovidiu</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-09-00182">1</xref>
<xref ref-type="aff" rid="af4-jcm-09-00182">4</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lupan</surname>
<given-names>Iulia</given-names>
</name>
<xref ref-type="aff" rid="af5-jcm-09-00182">5</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Deleanu</surname>
<given-names>Diana</given-names>
</name>
<xref ref-type="aff" rid="af3-jcm-09-00182">3</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Irimie</surname>
<given-names>Alexandru</given-names>
</name>
<xref ref-type="aff" rid="af6-jcm-09-00182">6</xref>
<xref ref-type="aff" rid="af7-jcm-09-00182">7</xref>
<xref ref-type="author-notes" rid="fn1-jcm-09-00182"></xref>
</contrib>
</contrib-group>
<aff id="af1-jcm-09-00182">
<label>1</label>
11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
<email>dr.geni@yahoo.co.uk</email>
(D.S.);
<email>calincainap2015@gmail.com</email>
(C.C.);
<email>obalacescu@yahoo.com</email>
(O.B.)</aff>
<aff id="af2-jcm-09-00182">
<label>2</label>
Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania;
<email>havasi.andrei@gmail.com</email>
(A.H.);
<email>cburz@yahoo.fr</email>
(C.B.)</aff>
<aff id="af3-jcm-09-00182">
<label>3</label>
Department of Immunology and Allergology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400162 Cluj-Napoca, Romania;
<email>deleanudiana@yahoo.com</email>
</aff>
<aff id="af4-jcm-09-00182">
<label>4</label>
Department of Functional Genomics, Proteomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania</aff>
<aff id="af5-jcm-09-00182">
<label>5</label>
Department of Molecular Biology and Biotehnology, Babeș-Bolyai University, 400084 Cluj-Napoca, Romania</aff>
<aff id="af6-jcm-09-00182">
<label>6</label>
11th Department of Oncological Surgery and Gynecological Oncology, “IuliuHatieganu” University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania;
<email>airimie@umfcluj.ro</email>
</aff>
<aff id="af7-jcm-09-00182">
<label>7</label>
Department of Surgery, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania</aff>
<author-notes>
<corresp id="c1-jcm-09-00182">
<label>*</label>
Correspondence:
<email>Gabriel.Samasca@gmail.com</email>
</corresp>
<fn id="fn1-jcm-09-00182">
<label></label>
<p>All authors contributed equally to this work.</p>
</fn>
</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>9</volume>
<issue>1</issue>
<elocation-id>182</elocation-id>
<history>
<date date-type="received">
<day>24</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>Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient’s T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient’s body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.</p>
</abstract>
<kwd-group>
<kwd>Chimeric antigen receptor (CAR)T-cell</kwd>
<kwd>colorectal cancer</kwd>
<kwd>immunotherapy</kwd>
<kwd>toxicity</kwd>
<kwd>trials</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<fig id="jcm-09-00182-f001" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<p>Overview of chimeric antigen receptor (CAR) T-cell therapy. Process of extracting normal T-cells from the patient’s peripheral blood; integration of CARs in T-cells in the laboratory; in vitro cultivation and expansion of CAR T-cells that are re-infused into the patient’s bloodstream; CAR T-cells proliferate and kill the tumor cells that bear the specific antigen the CARs are directed against.</p>
</caption>
<graphic xlink:href="jcm-09-00182-g001"></graphic>
</fig>
<fig id="jcm-09-00182-f002" orientation="portrait" position="float">
<label>Figure 2</label>
<caption>
<p>Targets for CAR T-cell therapy in CRC: Anti-4-1BB; CEA; guanylylcyclase2C (GUCY2C); TAG-72; EpCAM; epithelial glycoprotein 40(EGP40); NKG2D; HER-2; interferon alpha and beta receptor subunit 1(IFNAR1); prominin-1 (CD133); epithelial glycoprotein-2 (EGP-2).</p>
</caption>
<graphic xlink:href="jcm-09-00182-g002"></graphic>
</fig>
<table-wrap id="jcm-09-00182-t001" orientation="portrait" position="float">
<object-id pub-id-type="pii">jcm-09-00182-t001_Table 1</object-id>
<label>Table 1</label>
<caption>
<p>Ongoing clinical trials of CAR T-cell therapy conducted in CRC.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Pathology</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Trial ID</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Phase</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Administration</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Patient Number</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Year</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">EGFR IL-12</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Metastatic colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03542799</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2018</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B127-jcm-09-00182" ref-type="bibr">127</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">EGFR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">EGFR-positive colorectal Cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03152435</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2017</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B128-jcm-09-00182" ref-type="bibr">128</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NKG2D</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Metastatic colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03692429</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">36</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2018</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B126-jcm-09-00182" ref-type="bibr">126</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CEA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Metastatic colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02959151</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Vascular interventional therapy or intratumoral injection</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2016</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B129-jcm-09-00182" ref-type="bibr">129</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NKR-2</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Unresectable liver metastasis of colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03370198</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hepatic transarterial</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">18</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2017</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B130-jcm-09-00182" ref-type="bibr">130</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NKR-2</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Potentially resectable liver metastasis of colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03310008</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">36</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2017</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B131-jcm-09-00182" ref-type="bibr">131</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MUC 1</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02617134</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2015</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B132-jcm-09-00182" ref-type="bibr">132</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HER2</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02713984</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">60</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2016</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B133-jcm-09-00182" ref-type="bibr">133</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CEA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02349724</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">75</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2015</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B134-jcm-09-00182" ref-type="bibr">134</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CEA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Peritoneal metastases or malignant ascites of Colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03682744</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Intraperitoneal infusion</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">18</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2018</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B135-jcm-09-00182" ref-type="bibr">135</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">C-MET</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03638206</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">73</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2018</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B136-jcm-09-00182" ref-type="bibr">136</xref>
]</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">EpCAM</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Colorectal cancer</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">NCT03013712</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">I/II</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Vascular interventional therapy</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">60</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">2017</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">[
<xref rid="B137-jcm-09-00182" ref-type="bibr">137</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Endoscopy mediated infusion</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CD133</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02541370</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2015</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B138-jcm-09-00182" ref-type="bibr">138</xref>
]</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">CEA</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">CEA + liver metastases from gastrointestinal tumors including colorectal cancer</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">NCT02850536</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">I</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hepatic transarterial</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">5</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">2015</td>
<td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">[
<xref rid="B139-jcm-09-00182" ref-type="bibr">139</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Intrapancreatic retrograde venous infusion</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HER2</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03740256</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Systemic &Intratumoral</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">39</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2018</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B140-jcm-09-00182" ref-type="bibr">140</xref>
]</td>
</tr>
<tr>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CEA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CEA + adenocarcinoma with liver metastases from gastrointestinal tumors including colorectal cancer</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02416466</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hepatic transarterial administration</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2015</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[
<xref rid="B141-jcm-09-00182" ref-type="bibr">141</xref>
]</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
</record>

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