{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:18:23Z","timestamp":1785403103922,"version":"3.56.0"},"reference-count":82,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["70113306"],"award-info":[{"award-number":["70113306"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"award":["70113306"],"award-info":[{"award-number":["70113306"]}],"id":[{"id":"https:\/\/ror.org\/01wxdd722","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Hungarian Government","doi-asserted-by":"publisher","award":["2022-1.1.1-KK-2022-00005"],"award-info":[{"award-number":["2022-1.1.1-KK-2022-00005"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Hungarian Government","doi-asserted-by":"publisher","award":["HUN-REN RGH151414"],"award-info":[{"award-number":["HUN-REN RGH151414"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU\u2019s Horizon 2020 Research and Innovation Program","award":["739593"],"award-info":[{"award-number":["739593"]}]},{"DOI":"10.13039\/501100001656","name":"Helmholtz Initiative and Networking Fund","doi-asserted-by":"publisher","award":["InterLabs-0031"],"award-info":[{"award-number":["InterLabs-0031"]}],"id":[{"id":"10.13039\/501100001656","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helmholtz International Lab MHELTHERA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms27146407","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:32:54Z","timestamp":1784539974000},"page":"6407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel PSCA-Targeting Adapter Molecules for Late-Stage RevCAR-T Cell Therapy in Prostate Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1285-5052","authenticated-orcid":false,"given":"Claudia","family":"Arndt","sequence":"first","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"Mildred Scheel Early Career Center, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Garc\u00eda de Andres","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology\u2014HUN-REN TKI, Semmelweis University, H-1094 Budapest, Hungary"},{"name":"Hungarian Centre of Excellence for Molecular Medicine, In Vivo Imaging Advanced Core Facility, H-6723 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Mitwasi","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0646-5808","authenticated-orcid":false,"given":"Christin","family":"Neuber","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla E. G.","family":"Soto","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-5174","authenticated-orcid":false,"given":"Nathalia","family":"Jones-Cifuentes","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"School of Medicine, Department of Basic Sciences, Universidad Industrial de Santander, Bucaramanga 680002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5051-4114","authenticated-orcid":false,"given":"Alexandra","family":"von Jutrzenka-Trzebiatowski","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana R.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7343-0413","authenticated-orcid":false,"given":"Domokos","family":"Math\u00e9","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology\u2014HUN-REN TKI, Semmelweis University, H-1094 Budapest, Hungary"},{"name":"Hungarian Centre of Excellence for Molecular Medicine, In Vivo Imaging Advanced Core Facility, H-6723 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany"},{"name":"National Center for Tumor Diseases (NCT), NCT\/UCC Dresden, A Partnership Between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology & Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Feldmann","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany"},{"name":"National Center for Tumor Diseases (NCT), NCT\/UCC Dresden, A Partnership Between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology & Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cicchetti, R., Basconi, M., Litterio, G., Orsini, A., Mascitti, M., Digiacomo, A., Salzano, G., T\u0103taru, O.S., Ferro, M., and Giulioni, C. 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