A novel chimeric antigen receptor (CAR) T-cell therapy targeting CD38 may be an effective option for multiple myeloma (MM), according to research published in Frontiers in Oncology.

CAR-T cell therapy has encouraging clinical results in hematologic malignancies, including MM. CD38 antigen is an ideal target for MM immunotherapy because it is highly and uniformly expressed in myeloma cells. However, MM still remains incurable and many patients relapse.

The study authors used 2 human single-chain variable region (ScFv)-derived, second-generation CAR-T cells that target CD38 to evaluate their role as a potential therapy for MM. Most current CAR-T cells contain mouse-derived ScFv, which may reduce efficacy.


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The authors used a second-generation CAR structure and CD28 as the intracellular stimulation. They then integrated CD38 CARS into the genome of mitotic T-cells with a retroviral vector, the study explains.

The study performed an in vitro tumor killing experiment, which found that the CD38 CAR-T cells had rapid and efficient antitumor capability. The CD38 CAR-T cells also proliferated and expanded rapidly in vitro. In a mouse model, the CD38 CAR-T cells also had lasting antitumor effects, inhibiting tumor progression.

The CD38 CAR-T cells did not exhibit the same tumor-killing effect on CD38-negative tumor cells.

“CD38 CAR-T cells could be activated by CD38-positive tumor cells but not by tumor cells that do not express CD38, which further confirms the killing specificity of this kind of CD38 CAR-T cell,” the authors wrote in their report.

Based on these results, which are consistent with other studies, CD38 CAR-T therapy has the potential to be a novel therapeutic option for MM, warranting further study.

Reference

Li X, Feng Y, Shang F, et al. Characterization of the therapeutic effects of novel chimeric antigen receptor T cells targeting CD38 on multiple myeloma. Front Oncol. 2021;11:703087. doi:10.3389/fonc.2021.703087