Study Validates Presence of Immunotherapeutic Targets for Multiple Myeloma

A new study verified the presence of three different surface antigens on multiple myeloma (MM) cells. The research, presented at the European Society for Blood and Marrow Transplantation (EMBT)-(EHA) European Hematology Association Fifth European CAR-T-Cell Meeting, shows an emerging target for the development of novel chimeric antigen receptor (CAR) T-cell immunotherapies.

The three different surface antigens presented in the study include the following: (1) B-cell maturation antigen (BCMA), which is the main antigen targeted by currently available CAR-T treatments; (2) Fc receptor-like 5 (FCRL5), which has also been used as a target of antibody-drug conjugates for the treatment of MM; and (3) endothelin receptor B (ETRB), a novel tumor-specific antigen that represents a new tumoral target that may lead to development of new CAR-T immunotherapies.

Mégane Jassin, a doctoral student at the University of Liège in Belgium, and colleagues presented their findings during the EBMT-EHA conference.

The researchers quantified BCMA in seven MM cell lines using the Becton Dickinson Quantibrite Beads-PE kit, with the MM cell line OPM-2 used as a negative control. As a positive control, MM cell lines were incubated with a γ-secretase inhibitor to prevent natural cleavage of BCMA on the cell surface, which resulted in higher cell surface BCMA expression in the tested cell lines.

The presence of FCRL5 was also validated on twenty MM patient bone marrow samples with almost 100% expression frequency.

Finally, the researchers performed a proteomic analysis on six different MM cell lines to uncover ETRB, a novel tumor-specific antigen that represents a new tumoral target. ETRB was successfully validated on three MM patients’ bone marrow samples using flow cytometry. The gating strategy for ETRB validation involved isolation of the patient plasmocytes (CD38 and CD56 double-positive) followed by selection of ETRB-positive patient tumoral plasmocytes in comparison with the immunoglobulin control.

“In conclusion, this data validates that BCMA, ETRB and FCRL5 are localized to the tumoral plasmocytes’ cell surface,” the authors wrote, noting that ETRB could emerge as a target for the development of new CAR-T immunotherapies.

Reference

Jassin M, Köse MC, Marcion G, et al. Evaluation of new immunotherapeutic targets for multiple myeloma. Presented at the European Society for Blood and Marrow Transplantation-European Hematology Association Fifth European CAR-T cell Meeting; February 9-11, 2023; Rotterdam, Netherlands.