Journal Article

DKFZ-2026-01872

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Novel PSCA-Targeting Adapter Molecules for Late-Stage RevCAR-T Cell Therapy in Prostate Cancer.

Arndt, C. ; García de Andres, I. ; Bergmann, R. ; Mitwasi, N. ; Neuber, C. ; Soto, K. E. G. ; Jones-Cifuentes, N. ; von Jutrzenka-Trzebiatowski, A. ; Loureiro, L. R. ; Mathé, D. ; Bachmann, M.DKFZ* ; Feldmann, A.DKFZ*

2026
Molecular Diversity Preservation International Basel

Abstract: Chimeric antigen receptor (CAR) therapies are emerging as promising strategies, particularly for metastatic castration-resistant prostate cancer (PCa), as they can act independently of the androgen receptor axis. Adapter CAR-T cell platforms, such as the RevCAR system, offer precise therapeutic control and tumor targeting via small, rapidly eliminated tumor-specific adapters. To enable more convenient late-stage RevCAR-T therapy in PCa patients, allowing for discontinuous reverse target module (RevTM) infusion, we developed novel, larger IgG4-based RevTMs targeting prostate stem cell antigen (PSCA) and benchmarked them against previously described smaller adapter formats. Within the RevCAR system, PSCA-IgG4 RevTMs effectively mediated PCa killing at low effector-to-target ratios and low RevTM concentrations in a strictly antigen-dependent manner. Oncolytic activity was accompanied by a rapid and pronounced release of proinflammatory cytokines across a broad RevTM concentration range, which is particularly advantageous for immunologically cold PCa. Finally, anti-tumor activity was confirmed in a short-term mouse model. Preliminary PET studies further indicate slow blood elimination and tumor-specific accumulation of novel IgG4-RevTMs. Together, these data position PSCA-IgG4 RevTMs as promising candidates for stepwise RevCAR-T treatment in PCa, in which short-lived scFv-RevTMs are initially used to ensure a rapid safety switch, followed by larger IgG4-RevTMs once the risk profile is known.

Keyword(s): CAR-T cells ; PSCA ; RevCAR ; immunotherapy ; prostate cancer

Note: #DKTKZFB9# / #NCTZFB9#

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)
2. Koordinierungsstelle NCT Dresden (DD04)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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