Analysis of in vitro cytotoxicity of human NK cell line co-expressing a PSMA-specific CAR and an antitumor agent lactaptin

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Abstract

Development of efficient antitumor modalities remains a priority of modern translation medicine. Adoptive transfer of autologous T cells expressing chimeric antigen receptors (CARs) specific for tumor-associated surface targets of B cells has demonstrated encouraging results in recent clinical trials. It is tempting therefore to adapt this approach to solid cancers and move it to universal/allogeneic formats. For this reason, it appears very attractive to use human NK cell lines as CAR carriers. Using lentiviral delivery, human NK cell line YT was modified to express a PSMA-specific CAR and to produce an anticancer peptide lactaptin. "Armored” CAR-YT-Lact cell line obtained shows cytotoxicity against PSMA-positive prostate adenocarcinoma cells. Accordingly, YT-Lact cells display a moderate and non-specific activity against PSMA-negative target cells, which may translate into a tighter control of tumor cell escape via antigen loss.

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About the authors

T. N Belovezhets

Institute of Molecular and Cellular Biology, SB of the RAS; Novosibirsk State University

DA. Matvienko

Institute of Molecular and Cellular Biology, SB of the RAS; Novosibirsk State University

O. Y Volkova

Institute of Molecular and Cellular Biology, SB of the RAS

OA. A Koval

Novosibirsk State University; Institute of Chemical Biology and Fundamental Medicine, SB of the RAS

A. V Tkachenko

Institute of Chemical Biology and Fundamental Medicine, SB of the RAS

E. V Kuligina

Institute of Chemical Biology and Fundamental Medicine, SB of the RAS

A. V Taranin

Institute of Molecular and Cellular Biology, SB of the RAS; Novosibirsk State University

VA. Richter

Institute of Chemical Biology and Fundamental Medicine, SB of the RAS

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