Anti-CD19 Monoclonal antibody, clone 2E4 [PE/Cy5.5®]

Chimeric antigen receptor (CAR)-based immunotherapy has achieved dramatic success in the treatment of B cell malignancies, based on the summary of current research data, and has shown good potential in early phase cancer clinical trials. Modified constructs are being optimized to recognize and destroy tumor cells more effectively. By targeting the proper B-lineage-specific antigens such as CD19 and CD20, adoptive immunotherapy has demonstrated promising clinical results and already plays a role in the treatment of several lymphoid malignancies, which highlights the importance of target selection for other CAR therapies. The high efficacy of CAR-T cells has resulted in the approval of anti-CD19-directed CAR-T cells for the treatment of B cell malignancies. In this review, we focus on the basic structure and current clinical application of CAR-T cells, detail the research progress of CAR-T for different antigenic targets in hematological malignancies, and further discuss the current barriers and proposed solutions, investigating the possible mechanisms of recurrence of CAR-T cell therapy. A summary of the paper is also given to overview as the prospects for this therapy.

Autologous T cells engineered to express a chimeric antigen receptor (CAR) against the CD19 antigen are in the frontline of contemporary hemato-oncology therapies, leading to high remission rates in B-cell malignancies. Although effective, major obstacles involve the complex and costly individualized manufacturing process, and CD19 target antigen loss or modulation leading to resistant and relapse following CAR therapy. A potential solution for these limitations is the use of donor-derived gamma delta T cells as a CAR backbone. gamma delta T cells lack allogenecity and are safely used in haploidentical transplants. Moreover, gamma delta T cells are known to mediate natural anti-tumor responses. Here, we describe a 14-day production process initiated from peripheral-blood mononuclear cells, leading to a median 185-fold expansion of gamma delta T cells with high purity (>98% CD3+ and >99% gamma delta TCR+). CAR transduction efficacy of gamma delta T cells was equally high when compared to standard CAR-T cells (60.5 +/- 13.2 and 65.3 +/- 18.3%, respectively). CD19-directed gamma delta CAR-T cells were effective against CD19+ cell linesin vitroand in vivo, showing cytokine production, direct target killing, and clearance of bone marrow leukemic cells in an NSG model. Multiple injections of gamma delta CAR-T cells and priming of mice with zoledronate lead to enhanced tumor reductionin vivo. Unlike standard CD19 CAR-T cells, gamma delta CAR-T cells were able to target CD19 antigen negative leukemia cells, an effect that was enhanced after priming the cells with zoledronate. In conclusion, gamma delta CAR-T cell production is feasible and leads to highly pure and efficient effector cells. gamma delta CAR-T cell may provide a promising platform in the allogeneic setting, and may target leukemic cells also after antigen loss.