Patients with refractory and/or recurrent cancer have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators attempt to use T cells genetically modified to express a 4th generation lentiviral anti-PSMA/CD70 bi-specific chimeric antigen receptor (bi-4SCAR-PSMA/CD70). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD70 or PSMA, which is expressed at high levels on tumor cells but not at significant levels on normal tissues.~CD70 is a promising therapeutic target due to its restricted expression in normal tissues and overexpression in malignant tissues. Expression of CD70 was observed on multiple tumor types including kidney, breast, esophageal, liver, colon cancer, glioma, lymphoma as well as melanoma. In addition, it has been reported that anti-CD70 CAR T-cell therapy eliminated primary CD70-positive cells and had strong anti-tumor effects in preclinical animal models. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibit a higher affinity and antitumor effect against CD70+ tumor cells.~Prostate-specific membrane antigen (PSMA) is expressed in normal prostate and upregulated in prostate tumor. However, PSMA is not restricted to prostate cancer and it is known that PSMA is enriched in the tumor stromal environment. Based on immunostaining, it is confirmed that PSMA is expressed in a variety of solid tumors, including brain tumor, neuroblastoma and some lymphomas. Therefore, PSMA is a promising target for immunotherapy of many types of cancer.~A potential strategy to prevent relapse due to antigen escape is to infuse T-cells capable of recognizing multiple antigens. To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific PSMA/CD70 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in CD70 and/or PSMA positive cancer patients.
The purpose of this study is to assess the feasibility, safety and efficacy of anti-PSMA/CD70 bi-specific CAR-T cell therapy in patients with CD70 and PSMA positive malignancies. Another goal of the study is to learn more about the function of the PSMA/CD70 bi-specific CAR-T cells and their persistency in patients.