Engineering of Humanized PSMA-Directed CAR T Cells for Potent and Specific Elimination of Prostate Cancer Cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17110%2F25%3AA2603DB8" target="_blank" >RIV/61988987:17110/25:A2603DB8 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/2073-4409/14/17/1333" target="_blank" >https://www.mdpi.com/2073-4409/14/17/1333</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells14171333" target="_blank" >10.3390/cells14171333</a>

Result language

angličtina

Original language name

Engineering of Humanized PSMA-Directed CAR T Cells for Potent and Specific Elimination of Prostate Cancer Cells

Original language description

Chimeric Antigen Receptor (CAR) T cell therapy has achieved high response rates in patients with relapsed or refractory hematologic malignancies. However, comparable efficacy in solid tumors remains limited, partly due to poor CAR T cell persistence and immune-mediated rejection. A major contributor, which has hampered the clinical efficacy of CAR T cells in clinical practice, is the immunogenicity of the murine-derived single-chain variable fragments (scFvs) commonly used in CAR constructs. Cell and humoral immune responses to the murine parts of CARs have been implicated in CAR T cell rejection. Here, we describe the generation and in vitro characterization of humanized CAR T cells targeting prostate-specific membrane antigen (PSMA) on prostate cancer cells, based on two distinct murine scFvs (A5 and D7). Humanization improved the germinality index and successfully preserved CAR surface expression. Functional assays demonstrated that humanized PSMA-CAR T cells retained antigen-specific binding, activation and cytotoxicity, differentiation, exhaustion and cytokine secretion profiles comparable to their murine counterparts. These results support the feasibility of humanization as a strategy to reduce immunogenicity without compromising CAR T cell capabilities, providing a foundation for further in vivo validation in solid tumor settings.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/NW25-03-00298" target="_blank" >NW25-03-00298: Development of highly effective allogenic CAR T-cells based on innovative surface proteome analysis and non-viral approaches</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cells

ISSN

2073-4409

e-ISSN

2073-4409

Volume of the periodical

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Issue of the periodical within the volume

17

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

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UT code for WoS article

001569599800001

EID of the result in the Scopus database

2-s2.0-105015895288