Table 6 PSCA-based immunotherapy in preclinical and clinical settings
From: Significance of PSCA as a novel prognostic marker and therapeutic target for cancer
Method | Major findings | Reference/NCT |
|---|---|---|
DOTAGA-conjugated anti-PSCA IgG4-TM | Multimodal theranostic platform uses uniCAR T cell for in vivo imaging and immunoradiotherapy of prostate cancer. | [136] |
I131-PSCA-mAb | I131-PSCA-mAb inhibits cancer cell proliferation and enhances apoptosis in prostate cancer. | [139] |
PSCA-CAR T cell | Phase I study shows effective primary antitumor effects on metastatic castration-resistant prostate cancer (mCRPC) at 100 million dose plus lymphodepletion (LD) chemotherapy. | [140] |
PSA, PSCA, PSMA antigen | The high expression level of PSMA and PSCA is associated with an increase in the spread of prostate cancer, and it is possible to diagnose prostate cancer through peripheral blood with a combination of PSMA-PSA or PSCA-PSA antigens. | [141] |
PSCA-CAR T cell | Final results from phase I PSCA-targeted 4-1BB-co-stimulated CAR T cell therapy indicate antitumor activity against mCRPC with dose-limiting toxicities (DLT) of cystitis and LD was required for T cell expansion and activity. | [142] |
LU-Labeled PSCA antigen-specific monoclonal antibody | Due to the stable cell binding and specific accumulation in PSCA-positive tumor cells, radioimmnotherapy and imaging of prostate cancer is feasible using anti-PSCA monoclonal antibody. | [143] |
UniCAR T cells | Due to its self-regulating capacity, UniCAR T cell can be selectively activaited by multiple target modules (TMs) such as binding to PSCA, which provoke release of pro-inflammatory cytokines, and PCa cell lysis both in vitro and in vivo. | [144] |
Anti-PSCA CAR-T cells | Anti-PSCA CAR-T cells, specifically eliminated target tumor cells both in vivo and ex vivo and have the potential to treat patients with GC cancer in the clinic. | [145] |
Engineered humanized anti-PSCA A2 scFv-Fc2 antibody with double mutation (A2DM, t1/2 12 h | Therapy with 177 Lu-A2DM in mice bearing KPC-hPSCA expressing pancreatic ductal adenocarcinoma (PDAC) showed marked reduction of tumor size to 105 ± 63 mm3 compared 1143 ± 754 mm3 for saline-treated at day 25. | [146] |
Tandem (Tan) CAR-T targeting MUC1 and PSCA | Tan CAR T cell therapy has therapeutic effect in NSCLC and has a preclinical rationale for combination with anti-PD-1 antibody. | [147] |
CAR-NK-92 cells | PSCA CAR-NK-92 cells show good anti-tumor effect on PSCA+ tumor cells both in vitro and in vivo, and has the potential to be a therapeutic strategy for cervical cancer. | [148] |
α-RIT with 211At-labeled anti-PSCA A11 minibody | α-radioimmunotherapy (RIT) with astatine 211-labeled anti-PSCA A11 minibody, showed strong growth inhibition on both macrotumors and intratibial microtumors and promising treatment for micro metastatic and minimal residual disease of prostate cancer. | [149] |
124I-A11 PSCA minibody | Phase I study in subjects with metastatic bladder, prostate and pancreatic cancer, 2013-2017 | NCT02092948 |
PSCA-targeted CAR-T cells (BPX-601) | Phase I-II study on safety and activity of BPX therapy in patients with advanced solid tumors, 2016-2025 | NCT02744287 |
PSCA-CAR T cells | Phase I study of PSCA CAR T cell therapy in PSCA+ metastatic castration-resistant prostate cancer, 2009-2023 | NCT03873805 |