CD19/70 Bi-specific CAR-T Cell Therapy

B Cell Malignancies

CAR-T, B cell Malignancies, CD19, CD70

The purpose of this study is to assess the feasibility, safety and efficacy of CD19/70 bi-specific CAR-T cell therapy in patients with CD19 and/or CD70 positive B cell malignancies. Another goal of the study is to learn more about the safety and function of the anti-CD19/70 bi-specific CAR-T cells and their persistency in patients.

Important Regulatory Notice: This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China. ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities. Patients with refractory and/or recurrent B cell malignancies have poor prognosis despite complex multimodal therapy. Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Further, more than 40% patients with progressive large B cell lymphoma (LBCL) experienced reduced or lost expression of CD19 on the tumor cells after CAR19 treatment; low surface CD19 density before treatment was associated with progressive disease. Therefore, novel curative approaches are needed. The investigation attempts to use genetically modified T cells to express a 4th generation lentiviral anti-CD19/70 bi-specific CAR (bi-4SCAR-CD19/70). The CAR molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD19 or CD70, which is expressed at high levels on tumor cells but not at significant levels on normal tissues. CD70 is highly expressed in many cancers, but limited in normal tissues, it is a potential CAR-T therapeutic target. Expression of CD70 was observed on multiple tumor types including solid tumor as well as B cell malignancies. In addition, it has been reported that anti-CD70 CAR T-cells can eliminate CD70-positive cells and exhibit strong anti-tumor effects in preclinical animal models. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibited a higher affinity and antitumor effect against CD70-positive tumor cells. 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 CD19/70 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory B cell cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in CD19 and/or CD70 positive cancer patients.

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