Abstract P31: Design and Development of a Novel Anti-BCMA.ECD Antibody for Live Cell Therapy in Multiple Myeloma (MM)

Purpose: Multiple myeloma is characterized by the expansion of malignant plasma cells in the bone marrow (BM), which is associated with excessive production of monoclonal immunoglobulins in blood and urine in patients. The addition of monoclonal antibodies as immunotherapies in MM has further improved patient outcome. However, MM remains incurable for most patients, since drug-resistant clones constantly emerge and evolve. BCMA has been found to be overexpressed in MM and is being explored as a target for both antibody based and live cell therapy. Method: BCMA expression in MM patients was quantified using RQ PCR, and soluble BCMA was quantified using ELISA. The consensus BCMA.ECD sequence was cloned into a vector, sequenced, and protein expression was carried out using the Expi293 system, characterized by SDS-PAGE. Mice were immunized, and hybridoma cells were generated for the production of Anti-BCMA.ECD antibodies, which were further purified and characterized using western-blotting and other assays. The best binders were identified, and the ScFv sequence was incorporated into a novel second-generation CAR (Chimeric Antigen Receptor) T-cell, which was screened using flow-cytometry. Results: We characterized BCMA expression in a cohort of MM patients and found it to be elevated at the mRNA level. Serum or soluble BCMA levels were also elevated, predicting inferior therapeutic outcomes in MM patients. BCMA was validated as a candidate for Anti-BCMA therapy. BCMA.ECD protein was expressed in a eukaryotic system and used to generate hybridomas, resulting in twenty different clones. These clones were screened for the best binders, characterized by their binding affinity to BCMA.ECD protein using ELISA. The best binder (9C4) was used for deciphering the ScFv sequence for the development of a novel second-generation CAR. Conclusion: This study led to the characterization of BCMA expression and variation in Indian MM patients and the development of an Anti-BCMA antibody for a second-generation CAR. Citation Format: Gunjan Dagar, Ashna Gupta, Ravi Chauhan, Kalpana Luthra, Mayank Singh. Design and Development of a Novel Anti-BCMA.ECD Antibody for Live Cell Therapy in Multiple Myeloma (MM) [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl):Abstract nr P31.