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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/NW25-03-00298" target="_blank" >NW25-03-00298: Vývoj vysoce efektivních alogenních CAR T-buněk založený na inovativní povrchové proteomické analýze a ne-virálních přístupech</a><br>

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Cells

ISSN

2073-4409

e-ISSN

2073-4409

Svazek periodika

—

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

—

Kód UT WoS článku

001569599800001

EID výsledku v databázi Scopus

2-s2.0-105015895288