Next Article in Journal
Astrocytopathy Is Associated with CA1 Synaptic Dysfunction in a Mouse Model of Down Syndrome
Previous Article in Journal
Beyond Circadian Patterns: Mechanistic Insights into Sleep–Epilepsy Interactions and Therapeutic Implications
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cells
Volume 14
Issue 17
10.3390/cells14171333
cells-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Tobias D. Deller
1,2,3,
Jamal Alzubi
1,2,4,
Laura Mosti
1,†,
Marie Peschers
3,5,6,
Christian Gratzke
3,5,
Philipp Wolf
3,5 and
Toni Cathomen
1,2,3,*
1
Institute for Transfusion Medicine and Gene Therapy, Medical Center-University of Freiburg, 79106 Freiburg, Germany
2
Center for Cell and Gene Therapy, Medical Center-University of Freiburg, 79106 Freiburg, Germany
3
Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
4
Department of Haematooncology, Faculty of Medicine, University of Ostrava, 70852 Ostrava, Czech Republic
5
Department of Urology, Medical Center-University of Freiburg, 79106 Freiburg, Germany
6
Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany
*
Author to whom correspondence should be addressed.
†
Current address: AGC Biologics S.p.A., 20091 Bresso, MI, Italy.
Cells 2025, 14(17), 1333; https://doi.org/10.3390/cells14171333
Submission received: 2 August 2025 / Revised: 22 August 2025 / Accepted: 25 August 2025 / Published: 28 August 2025
(This article belongs to the Special Issue CAR T Cells in Human Cancers)
Review Reports Versions Notes

Abstract

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.
Keywords: CAR T cells; immunogenicity; humanization; prostate cancer; prostate-specific membrane antigen; T cell activation; T cell differentiation; T cell exhaustion CAR T cells; immunogenicity; humanization; prostate cancer; prostate-specific membrane antigen; T cell activation; T cell differentiation; T cell exhaustion

Share and Cite

MDPI and ACS Style

Deller, T.D.; Alzubi, J.; Mosti, L.; Peschers, M.; Gratzke, C.; Wolf, P.; Cathomen, T. Engineering of Humanized PSMA-Directed CAR T Cells for Potent and Specific Elimination of Prostate Cancer Cells. Cells 2025, 14, 1333. https://doi.org/10.3390/cells14171333

AMA Style

Deller TD, Alzubi J, Mosti L, Peschers M, Gratzke C, Wolf P, Cathomen T. Engineering of Humanized PSMA-Directed CAR T Cells for Potent and Specific Elimination of Prostate Cancer Cells. Cells. 2025; 14(17):1333. https://doi.org/10.3390/cells14171333

Chicago/Turabian Style

Deller, Tobias D., Jamal Alzubi, Laura Mosti, Marie Peschers, Christian Gratzke, Philipp Wolf, and Toni Cathomen. 2025. "Engineering of Humanized PSMA-Directed CAR T Cells for Potent and Specific Elimination of Prostate Cancer Cells" Cells 14, no. 17: 1333. https://doi.org/10.3390/cells14171333

APA Style

Deller, T. D., Alzubi, J., Mosti, L., Peschers, M., Gratzke, C., Wolf, P., & Cathomen, T. (2025). Engineering of Humanized PSMA-Directed CAR T Cells for Potent and Specific Elimination of Prostate Cancer Cells. Cells, 14(17), 1333. https://doi.org/10.3390/cells14171333

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Article metric data becomes available approximately 24 hours after publication online.
Back to TopTop