{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:40:37Z","timestamp":1785404437435,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,8]]},"group-title":"Bioengineering","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["P30CA033572"],"award-info":[{"award-number":["P30CA033572"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Adoptive cell therapies used to treat advanced prostate cancer are being developed to target several tumor-associated antigens, including prostate-specific membrane antigen (PSMA). Chimeric antigen receptor (CAR) T cell therapy using the single chain variable fragment (scFv) derived from the humanized murine mAb clone, J591, as the antigen-binding domain has shown promising anti-tumor activity. However, it has also been associated with macrophage activation syndrome and other unwanted toxicities, highlighting the need for more specific and human-derived antigen-binders with optimized construct designs for improved safety and efficacy. Here, we optimize a human scFv-based PSMA-targeted CAR (hPSMA-CAR) with highly selective PSMA targeting. We further introduce a membrane-bound IL-12 (mbIL12) molecule, which enhances potency with increased T cell expansion, IFNy production and anti-tumor cell activity\n                  <jats:italic>in vitro<\/jats:italic>\n                  . Using two clinically-relevant bone-metastatic prostate cancer models, we show that mbIL12-engineered hPSMA-CAR T cells drive potent\n                  <jats:italic>in vivo<\/jats:italic>\n                  anti-tumor responses. In summary, we have developed a promising therapeutic that has potential to promote safe and effective treatment of advanced PSMA+ prostate cancer.\n                <\/jats:p>","DOI":"10.64898\/2026.03.05.709907","type":"posted-content","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:30:42Z","timestamp":1773030642000},"source":"Crossref","is-referenced-by-count":0,"title":["IL12-engineered human PSMA-CAR T cells for the treatment of advanced prostate cancer"],"prefix":"10.64898","author":[{"given":"Lupita S.","family":"Lopez","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, Keck School of Medicine (KSOM) of USC, Los Angeles, CA, 90033, USA"},{"name":"Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA"},{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 91010, 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