Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies.
Identifieur interne : 000218 ( Main/Exploration ); précédent : 000217; suivant : 000219Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies.
Auteurs : Fleury Augustin Nsole Biteghe [États-Unis] ; Neelakshi Mungra [Afrique du Sud] ; Nyangone Ekome Toung Chalomie [République populaire de Chine] ; Jean De La Croix Ndong [États-Unis] ; Jean Engohang-Ndong [États-Unis] ; Guillaume Vignaux [États-Unis] ; Eden Padayachee [États-Unis] ; Krupa Naran [Afrique du Sud] ; Stefan Barth [Afrique du Sud]Source :
- Oncotarget [ 1949-2553 ] ; 2020.
Abstract
The epidermal growth factor receptor (EGFR) has been recognized as an important therapeutic target in oncology. It is commonly overexpressed in a variety of solid tumors and is critically involved in cell survival, proliferation, metastasis, and angiogenesis. This multi-dimensional role of EGFR in the progression and aggressiveness of cancer, has evolved from conventional to more targeted therapeutic approaches. With the advent of hybridoma technology and phage display techniques, the first anti-EGFR monoclonal antibodies (mAbs) (Cetuximab and Panitumumab) were developed. Due to major limitations including host immune reactions and poor tumor penetration, these antibodies were modified and used as guiding mechanisms for the specific delivery of readily available chemotherapeutic agents or plants/bacterial toxins, giving rise to antibody-drug conjugates (ADCs) and immunotoxins (ITs), respectively. Continued refinement of ITs led to deimmunization strategies based on depletion of B and T-cell epitopes or substitution of non-human toxins leading to a growing repertoire of human enzymes capable of inducing cell death. Similarly, the modification of classical ADCs has resulted in the first, fully recombinant versions. In this review, we discuss significant advancements in EGFR-targeting immunoconjugates, including ITs and recombinant photoactivable ADCs, which serve as a blueprint for further developments in the evolving domain of cancer immunotherapy.
DOI: 10.18632/oncotarget.27730
PubMed: 33014289
PubMed Central: PMC7517958
Affiliations:
- Afrique du Sud, République populaire de Chine, États-Unis
- Californie, Guangdong, Kentucky, Maryland, Ohio, État de New York
- Jiangmen
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work.</wicri:noCountry></affiliation></author><author><name sortKey="Mungra, Neelakshi" sort="Mungra, Neelakshi" uniqKey="Mungra N" first="Neelakshi" last="Mungra">Neelakshi Mungra</name><affiliation wicri:level="1"><nlm:affiliation>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town</wicri:regionArea><wicri:noRegion>Cape Town</wicri:noRegion></affiliation><affiliation><nlm:affiliation>These authors contributed equally to this work.</nlm:affiliation><wicri:noCountry code="no comma">These authors contributed equally to this work.</wicri:noCountry></affiliation></author><author><name sortKey="Chalomie, Nyangone Ekome Toung" sort="Chalomie, Nyangone Ekome Toung" uniqKey="Chalomie N" first="Nyangone Ekome Toung" last="Chalomie">Nyangone Ekome Toung Chalomie</name><affiliation wicri:level="3"><nlm:affiliation>Sun Yat-Sen University, Zhongshan Medical School, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Sun Yat-Sen University, Zhongshan Medical School, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Ndong, Jean De La Croix" sort="Ndong, Jean De La Croix" uniqKey="Ndong J" first="Jean De La Croix" last="Ndong">Jean De La Croix Ndong</name><affiliation wicri:level="2"><nlm:affiliation>Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Orthopedic Surgery, 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Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town</wicri:regionArea><wicri:noRegion>Cape Town</wicri:noRegion></affiliation><affiliation><nlm:affiliation>These authors contributed equally to this work.</nlm:affiliation><wicri:noCountry code="no comma">These authors contributed equally to this work.</wicri:noCountry></affiliation></author><author><name sortKey="Barth, Stefan" sort="Barth, Stefan" uniqKey="Barth S" first="Stefan" last="Barth">Stefan Barth</name><affiliation wicri:level="1"><nlm:affiliation>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South 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uniqKey="Biteghe F" first="Fleury Augustin Nsole" last="Biteghe">Fleury Augustin Nsole Biteghe</name><affiliation wicri:level="2"><nlm:affiliation>Department of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical, Los Angeles, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical, Los Angeles, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation><nlm:affiliation>These authors contributed equally to this work.</nlm:affiliation><wicri:noCountry code="no comma">These authors contributed equally to this work.</wicri:noCountry></affiliation></author><author><name sortKey="Mungra, Neelakshi" sort="Mungra, Neelakshi" uniqKey="Mungra N" first="Neelakshi" last="Mungra">Neelakshi Mungra</name><affiliation wicri:level="1"><nlm:affiliation>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town</wicri:regionArea><wicri:noRegion>Cape Town</wicri:noRegion></affiliation><affiliation><nlm:affiliation>These authors contributed equally to this work.</nlm:affiliation><wicri:noCountry code="no comma">These authors contributed equally to this work.</wicri:noCountry></affiliation></author><author><name sortKey="Chalomie, Nyangone Ekome Toung" sort="Chalomie, Nyangone Ekome Toung" uniqKey="Chalomie N" first="Nyangone Ekome Toung" last="Chalomie">Nyangone Ekome Toung Chalomie</name><affiliation wicri:level="3"><nlm:affiliation>Sun Yat-Sen University, Zhongshan Medical School, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Sun Yat-Sen University, Zhongshan Medical School, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Ndong, Jean De La Croix" sort="Ndong, Jean De La Croix" uniqKey="Ndong J" first="Jean De La Croix" last="Ndong">Jean De La Croix Ndong</name><affiliation wicri:level="2"><nlm:affiliation>Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Orthopedic Surgery, New York University School of Medicine, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Engohang Ndong, Jean" sort="Engohang Ndong, Jean" uniqKey="Engohang Ndong J" first="Jean" last="Engohang-Ndong">Jean Engohang-Ndong</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biological Sciences, Kent State University at Tuscarawas, New Philadelphia, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biological Sciences, Kent State University at Tuscarawas, New Philadelphia, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Vignaux, Guillaume" sort="Vignaux, Guillaume" uniqKey="Vignaux G" first="Guillaume" last="Vignaux">Guillaume Vignaux</name><affiliation wicri:level="2"><nlm:affiliation>Arctic Slope Regional Corporation Federal, Beltsville, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Arctic Slope Regional Corporation Federal, Beltsville, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Padayachee, Eden" sort="Padayachee, Eden" uniqKey="Padayachee E" first="Eden" last="Padayachee">Eden Padayachee</name><affiliation wicri:level="2"><nlm:affiliation>Department of Physiology, University of Kentucky, Lexington, KY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Kentucky, Lexington, KY</wicri:regionArea><placeName><region type="state">Kentucky</region></placeName></affiliation></author><author><name sortKey="Naran, Krupa" sort="Naran, Krupa" uniqKey="Naran K" first="Krupa" last="Naran">Krupa Naran</name><affiliation wicri:level="1"><nlm:affiliation>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town</wicri:regionArea><wicri:noRegion>Cape Town</wicri:noRegion></affiliation><affiliation><nlm:affiliation>These authors contributed equally to this work.</nlm:affiliation><wicri:noCountry code="no comma">These authors contributed equally to this work.</wicri:noCountry></affiliation></author><author><name sortKey="Barth, Stefan" sort="Barth, Stefan" uniqKey="Barth S" first="Stefan" last="Barth">Stefan Barth</name><affiliation wicri:level="1"><nlm:affiliation>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town</wicri:regionArea><wicri:noRegion>Cape Town</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>South African Research Chair in Cancer Biotechnology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>South African Research Chair in Cancer Biotechnology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town</wicri:regionArea><wicri:noRegion>Cape Town</wicri:noRegion></affiliation><affiliation><nlm:affiliation>These authors contributed equally to this work.</nlm:affiliation><wicri:noCountry code="no comma">These authors contributed equally to this work.</wicri:noCountry></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The epidermal growth factor receptor (EGFR) has been recognized as an important therapeutic target in oncology. It is commonly overexpressed in a variety of solid tumors and is critically involved in cell survival, proliferation, metastasis, and angiogenesis. This multi-dimensional role of EGFR in the progression and aggressiveness of cancer, has evolved from conventional to more targeted therapeutic approaches. With the advent of hybridoma technology and phage display techniques, the first anti-EGFR monoclonal antibodies (mAbs) (Cetuximab and Panitumumab) were developed. Due to major limitations including host immune reactions and poor tumor penetration, these antibodies were modified and used as guiding mechanisms for the specific delivery of readily available chemotherapeutic agents or plants/bacterial toxins, giving rise to antibody-drug conjugates (ADCs) and immunotoxins (ITs), respectively. Continued refinement of ITs led to deimmunization strategies based on depletion of B and T-cell epitopes or substitution of non-human toxins leading to a growing repertoire of human enzymes capable of inducing cell death. Similarly, the modification of classical ADCs has resulted in the first, fully recombinant versions. In this review, we discuss significant advancements in EGFR-targeting immunoconjugates, including ITs and recombinant photoactivable ADCs, which serve as a blueprint for further developments in the evolving domain of cancer immunotherapy.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33014289</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>06</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1949-2553</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><Issue>38</Issue><PubDate><Year>2020</Year><Month>Sep</Month><Day>22</Day></PubDate></JournalIssue><Title>Oncotarget</Title><ISOAbbreviation>Oncotarget</ISOAbbreviation></Journal><ArticleTitle>Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies.</ArticleTitle><Pagination><MedlinePgn>3531-3557</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.18632/oncotarget.27730</ELocationID><Abstract><AbstractText>The epidermal growth factor receptor (EGFR) has been recognized as an important therapeutic target in oncology. It is commonly overexpressed in a variety of solid tumors and is critically involved in cell survival, proliferation, metastasis, and angiogenesis. This multi-dimensional role of EGFR in the progression and aggressiveness of cancer, has evolved from conventional to more targeted therapeutic approaches. With the advent of hybridoma technology and phage display techniques, the first anti-EGFR monoclonal antibodies (mAbs) (Cetuximab and Panitumumab) were developed. Due to major limitations including host immune reactions and poor tumor penetration, these antibodies were modified and used as guiding mechanisms for the specific delivery of readily available chemotherapeutic agents or plants/bacterial toxins, giving rise to antibody-drug conjugates (ADCs) and immunotoxins (ITs), respectively. Continued refinement of ITs led to deimmunization strategies based on depletion of B and T-cell epitopes or substitution of non-human toxins leading to a growing repertoire of human enzymes capable of inducing cell death. Similarly, the modification of classical ADCs has resulted in the first, fully recombinant versions. In this review, we discuss significant advancements in EGFR-targeting immunoconjugates, including ITs and recombinant photoactivable ADCs, which serve as a blueprint for further developments in the evolving domain of cancer immunotherapy.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Biteghe</LastName><ForeName>Fleury Augustin Nsole</ForeName><Initials>FAN</Initials><AffiliationInfo><Affiliation>Department of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical, Los Angeles, CA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>These authors contributed equally to this work.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mungra</LastName><ForeName>Neelakshi</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>These authors contributed equally to this work.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chalomie</LastName><ForeName>Nyangone Ekome Toung</ForeName><Initials>NET</Initials><AffiliationInfo><Affiliation>Sun Yat-Sen University, Zhongshan Medical School, Guangzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ndong</LastName><ForeName>Jean De La Croix</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Engohang-Ndong</LastName><ForeName>Jean</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Biological Sciences, Kent State University at Tuscarawas, New Philadelphia, OH, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vignaux</LastName><ForeName>Guillaume</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Arctic Slope Regional Corporation Federal, Beltsville, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Padayachee</LastName><ForeName>Eden</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Physiology, University of Kentucky, Lexington, KY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Naran</LastName><ForeName>Krupa</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>These authors contributed equally to this work.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barth</LastName><ForeName>Stefan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>South African Research Chair in Cancer Biotechnology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>These authors contributed equally to this work.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Oncotarget</MedlineTA><NlmUniqueID>101532965</NlmUniqueID><ISSNLinking>1949-2553</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">epidermal growth factor receptor (EGFR)</Keyword><Keyword MajorTopicYN="N">recombinant antibody photoimmunoconjugates (rAPCs)</Keyword><Keyword MajorTopicYN="N">recombinant antibody-drug conjugates (rADCs)</Keyword><Keyword MajorTopicYN="N">recombinant immunotoxins (ITs)</Keyword><Keyword MajorTopicYN="N">targeted human cytolytic fusion proteins (hCFPs)</Keyword></KeywordList><CoiStatement>CONFLICTS OF INTEREST The authors declare no conflicts of interest. Prof Barth is inventor on several patent applications describing EGFR specific PDT and hCFP. Most of these patents have been assigned to UCT.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>05</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>10</Month><Day>5</Day><Hour>6</Hour><Minute>18</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>10</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>10</Month><Day>6</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33014289</ArticleId><ArticleId IdType="doi">10.18632/oncotarget.27730</ArticleId><ArticleId IdType="pii">27730</ArticleId><ArticleId 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