PSMA/CD70 Bi-specific CAR-T Cell Therapy
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|ClinicalTrials.gov Identifier: NCT05437341|
Recruitment Status : Recruiting
First Posted : June 29, 2022
Last Update Posted : June 29, 2022
|Condition or disease||Intervention/treatment||Phase|
|Cancer Disease||Biological: bi-4SCAR PSMA/CD70 T cells||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||PSMA/CD70 Bi-specific CAR-T Cells for Cancer Treatment|
|Estimated Study Start Date :||June 30, 2022|
|Estimated Primary Completion Date :||December 31, 2025|
|Estimated Study Completion Date :||June 30, 2026|
|Experimental: bi-4SCAR-PSMA/CD70 T Cell Therapy for CD70 and/or PSMA positive cancer||
Biological: bi-4SCAR PSMA/CD70 T cells
Infusion of bi-4SCAR PSMA/CD70 T cells at 10^6 cells/kg body weight via IV
- Number of patients with adverse events. [ Time Frame: 6 months ]Determine the toxicity profile the bi-4SCAR PSMA/CD70 cells with Common Toxicity Criteria for Adverse Effects version 4.0
- Tumor remission response evaluation [ Time Frame: 1 year ]Objective complete response (CR) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
- Tumor remission response evaluation [ Time Frame: 1 year ]Objective partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
- The expansion of bi-4SCAR PSMA/CD70 T cells [ Time Frame: 1 year ]Scale of CAR copies (for efficacy)
- The persistence of bi-4SCAR PSMA/CD70 T cells [ Time Frame: 1 year ]Scale of tumor burden (for efficacy)
- Survival time of the patients [ Time Frame: 3 years ]The overall survival (OS) time of the patients treated with the bi-4SCAR PSMA/CD70 T cells will be evaluated
- Survival time of the patients [ Time Frame: 3 years ]The progression free survival (PFS) time of the patients treated with the bi-4SCAR PSMA/CD70 T cells will be evaluated
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05437341
|Contact: Lung-Ji Chang, PhDemail@example.com|
|Shenzhen Geno-immune Medical Institute||Recruiting|
|Shenzhen, Guangdong, China, 518000|
|Contact: Lung-Ji Chang, PhD 86-075586725195 firstname.lastname@example.org|