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Highly Efficient Targeting of EGFR-Expressing Tumor Cells with UniCAR T Cells via Target Modules Based on Cetuximab®.


ABSTRACT: 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 ?EGFR TMs: a nanobody (nb)-based ?EGFR TM derived from the camelid ?EGFR 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 ?EGFR 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 ?EGFR TMs.

SUBMITTER: Jureczek J 

PROVIDER: S-EPMC7297505 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Highly Efficient Targeting of EGFR-Expressing Tumor Cells with UniCAR T Cells via Target Modules Based on Cetuximab<sup>®</sup>.

Jureczek Justyna J   Feldmann Anja A   Bergmann Ralf R   Arndt Claudia C   Berndt Nicole N   Koristka Stefanie S   Loureiro Liliana Rodrigues LR   Mitwasi Nicola N   Hoffmann Anja A   Kegler Alexandra A   Bartsch Tabea T   Bachmann Michael M  

OncoTargets and therapy 20200612


<h4>Introduction</h4>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  ...[more]

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