PSCA-CAR T / City of Hope - LARVOL DELTA

Combining Radiopharmaceutical Therapy with CAR T cells to Overcome the Heterogeneous Immunosuppressive Prostate Tumor Microenvironment (SITC 2025) - P1 | "In a phase 1 clinical trial (NCT03873805) evaluating CAR-T cells targeting Prostate Stem Cell Antigen (PSCA), we observed promising safety and therapeutic responses in patients who underwent cyclophosphamide (Cy) lymphodepletion, but the several challenge must be addressed to improve overall responses: 1) antigen heterogeneity, and 2) the immunosuppressive tumor microenvironment (TME).2 Preclinical evidence suggests radiation enhances CAR T cell efficacy by priming the TME,3 4 yet focal radiation lacks the capability to target multi-metastatic disease systemically. The combination was well tolerated in the syngeneic mouse model, with favorable TME changes, enhanced therapeutic responses, and extended durability. By using the two therapies (177Lu-PSMA-617 and PSCA-CAR T cells) that are FDA approved or in clinical development, we aim for rapid translation of this combination strategy to patients with mCRPC and other advanced lethal cancer types."

Biomarker • CAR T-Cell Therapy • Heterogeneity • Tumor microenvironment • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • PSCA

Optimization of Safe and Effective PSCA-CAR/IL12 Engineered T cell Combinatorial Treatment Strategies Against Metastatic Prostate Cancer (PCF 2025) - "Mice were treated with PSCA-CAR/aPDL1-IL12, PSCA-CAR/mbIL12, or conventional PSCA-CAR T cells, with or without cyclophosphamide (Cy) preconditioning. The addition of fludarabine (Flu) to Cy was tested to evaluate synergistic conditioning effects...Funding Acknowledgements PCF Young Investigator Award 2021 (PI: Murad), PCF Tactical Award (PI: Pricman), Department of Defence Idea/Expansion Awards (PI: Priceman), Tower Cancer Research Foundation Career Development Award 2025 (PI: Murad) Conflict of Interest Statement There are no conflicts to report for data presented. INTERNAL"

Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IL12A • KRAS • PSCA • PTEN

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: May 2025 ➔ Apr 2026

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

Off-the-shelf invariant NKT cells expressing anti-PSCA CAR and IL-15 promote pancreatic cancer regression in mice. (PubMed, J Clin Invest) - "In multiple in vitro and in vivo PDAC models, freshly manufactured PSCA CAR_sIL-15 iNKT cells and frozen-thawed, off-the-shelf PSCA CAR_sIL-15 iNKT cells demonstrate comparable efficacies, and both show remarkable suppression of PSCA-positive and gemcitabine-resistant PDAC. Importantly, off-the-shelf cryopreserved PSCA CAR_sIL-15 iNKT cells show equivalent efficacy when compared with PSCA CAR T cells using the same PSCA CAR and in the same PDAC model; however, PSCA CAR_sIL-15 iNKT cells do not appear to induce systemic toxicity or graft-versus-host disease, thus allowing for multiple infusions to control recurrent disease. Collectively, our study suggests that PSCA CAR_sIL-15 iNKT cells merit clinical investigation for PDAC patients exhibiting positive PSCA expression. The therapy could be given as a single agent or in combination with established therapeutic modalities for PDAC."

Journal • Preclinical • Graft versus Host Disease • Hepatology • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • IL15 • PSCA

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ May 2025

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

City of Hope CAR T-Cell Therapy for Advanced Prostate Cancer Demonstrates Positive Results in Phase 1 Clinical Trial (OncLive) - P1b | N=21 | NCT05805371 | "Treating prostate cancer with immunotherapy is currently difficult to do. But preliminary results from a first-in-human phase 1 trial using a chimeric antigen receptor (CAR) T cell therapy developed by researchers from City of Hope...showed that patients with advanced prostate cancer had minimal side effects with the cellular immunotherapy and had promising therapeutic activity, according to a study published today in Nature Medicine...The trial treated 14 prostate stem cell antigen (PSCA)-positive patients who had metastatic castration-resistant prostate cancer (mCRPC)...Four out of 14 patients had declines in their PSA levels, which is a serum marker of disease progression in people with prostate cancer, including one patient with a significant decline. Imaging showed therapeutic responses in a subset of treated patients....Five out of 14 patients had mild or moderate cytokine release syndrome..."

Cytokine release syndrome • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor