Chimeric antigen receptor (CAR) T cell therapy has shown remarkable successes in fighting B cell leukemias/lymphomas and numerous CAR-T’s are being developed for use in multiple myeloma. While primising results have been reported with BCMA CAR T cells, responses do not appear to be durable. This highlights a need for additional therapies to treat multiple myeloma.
A study just published in Cancer Immunology Research, describes a CD138/CD38 dual-targeted CAR-T. The dual-CAR construct was carefully designed to target the MM-associated antigens, taking into consideration the distribution of both antigens on normal human tissues. CD138 is highly expressed on the surface of plasma cells and myeloma cells, and is important for adhesion and accumulating survival signals. The CD38 antigen is highly and uniformly expressed on plasma cells and thus represents an ideal target for the treatment of multiple myeloma.
The results demonstrated that the CD138/CD38-targeted dual CAR (dCAR138-38) elicited a potent anti-myeloma response both in-vitro and in vivo. NSG mice transplanted with a multiple myeloma cell line, and treated with dCAR138-38 showed median survival of 97 days compared to 31 days in the control group treated with mock-lymphocytes. The dCAR138-38 showed increased specificity toward cells expressing both targeted antigens compared to single-antigen-expressing cells, and low activity toward primary cells from healthy tissues.
dCAR138-38 may provide a potent and safe alternative therapy for multiple myeloma patients
Related Article: What are CAR-T Cells and Their Role in Multiple Myeloma
, , , et al. Treatment of Multiple Myeloma using Chimeric Antigen Receptor T Cells with Dual Specificity. Cancer Immunol Res. 2020 Oct 2;canimm.0118.2020. doi: 10.1158/2326-6066.CIR-20-0118. Online ahead of print.