Highly Efficient Targeting of EGFR-Expressing Tumor Cells with UniCAR T Cells via Target Modules Based on Cetuximab®
© 2020 Jureczek et al..
INTRODUCTION: Since epithelial growth factor receptor (EGFR) overexpression is linked to a variety of malignancies, it is an attractive target for immune therapy including chimeric antigen receptor (CAR)-engineered T cells. Unfortunately, CAR T cell therapy harbors the risk of severe, even life-threatening side effects. Adaptor CAR T cell platforms such as the previously described UniCAR system might be able to overcome these problems. In contrast to conventional CARs, UniCAR T cells are per se inert. Their redirection towards target cells occurs only in the presence of a tumor-specific target molecule (TM). TMs are bifunctional molecules being able to recognize a tumor-associated antigen and to cross-link the CAR T cell via a peptide epitope recognized by the UniCAR domain.
MATERIALS AND METHODS: Here, we compare αEGFR TMs: a nanobody (nb)-based αEGFR TM derived from the camelid αEGFR antibody 7C12 with a murine and humanized single-chain fragment variable (scFv) based on the clinically used antibody Cetuximab®.
RESULTS: In principle, both the nb- and scFv-based TM formats are able to redirect UniCAR T cells to eliminate EGFR-expressing tumor cells in an antigen-specific and TM-dependent manner. However, the scFv-based αEGFR TM was significantly superior to the nb-based TM especially with respect to lysis of tumor cells.
DISCUSSION: Improved efficiency of the scFv-based TM allowed the redirection of UniCAR T cells towards tumor cells expressing high as well as low EGFR levels in comparison to nb-based αEGFR TMs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
OncoTargets and therapy - 13(2020) vom: 01., Seite 5515-5527 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jureczek, Justyna [VerfasserIn] |
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| Links: |
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| Themen: |
Adaptor CARs |
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| Anmerkungen: |
Date Revised 15.04.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.2147/OTT.S245169 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM311847110 |
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| 520 | |a © 2020 Jureczek et al. | ||
| 520 | |a INTRODUCTION: Since epithelial growth factor receptor (EGFR) overexpression is linked to a variety of malignancies, it is an attractive target for immune therapy including chimeric antigen receptor (CAR)-engineered T cells. Unfortunately, CAR T cell therapy harbors the risk of severe, even life-threatening side effects. Adaptor CAR T cell platforms such as the previously described UniCAR system might be able to overcome these problems. In contrast to conventional CARs, UniCAR T cells are per se inert. Their redirection towards target cells occurs only in the presence of a tumor-specific target molecule (TM). TMs are bifunctional molecules being able to recognize a tumor-associated antigen and to cross-link the CAR T cell via a peptide epitope recognized by the UniCAR domain | ||
| 520 | |a MATERIALS AND METHODS: Here, we compare αEGFR TMs: a nanobody (nb)-based αEGFR TM derived from the camelid αEGFR antibody 7C12 with a murine and humanized single-chain fragment variable (scFv) based on the clinically used antibody Cetuximab® | ||
| 520 | |a RESULTS: In principle, both the nb- and scFv-based TM formats are able to redirect UniCAR T cells to eliminate EGFR-expressing tumor cells in an antigen-specific and TM-dependent manner. However, the scFv-based αEGFR TM was significantly superior to the nb-based TM especially with respect to lysis of tumor cells | ||
| 520 | |a DISCUSSION: Improved efficiency of the scFv-based TM allowed the redirection of UniCAR T cells towards tumor cells expressing high as well as low EGFR levels in comparison to nb-based αEGFR TMs | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a EGFR | |
| 650 | 4 | |a UniCAR | |
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| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a solid tumors | |
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| 700 | 1 | |a Arndt, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Berndt, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Koristka, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Loureiro, Liliana Rodrigues |e verfasserin |4 aut | |
| 700 | 1 | |a Mitwasi, Nicola |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann, Anja |e verfasserin |4 aut | |
| 700 | 1 | |a Kegler, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Bartsch, Tabea |e verfasserin |4 aut | |
| 700 | 1 | |a Bachmann, Michael |e verfasserin |4 aut | |
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