BCMA, CD38, CD3

Class

Trispecific T-cell engaging antibody

Pathway

T-cell redirection/engagement

This mechanism uses a trispecific antibody that simultaneously binds two proteins found on malignant plasma cells—BCMA (B-cell maturation antigen) and CD38—together with CD3, a signaling protein on T cells. By physically linking a patient's own T cells to tumor cells expressing either or both target antigens, the antibody triggers formation of an immune synapse that activates the T cell to kill the bound cancer cell, independent of the T cell's native antigen receptor. This class of molecule, known as a T-cell engager, is used mainly in multiple myeloma, a cancer of plasma cells, and related plasma cell disorders. Targeting two tumor antigens rather than one is intended to address antigen heterogeneity: myeloma cells can vary in how much BCMA or CD38 they display, and some may lose one marker over time. A dual-targeting engager can still recruit T cells to cells expressing only one of the two antigens, potentially broadening coverage and reducing the chance that antigen-low tumor populations escape treatment. The biological rationale for redirecting T cells in this disease rests on myeloma's known sensitivity to cytotoxic T-cell killing when engagement is forced pharmacologically, since these tumors do not reliably provoke a spontaneous immune response.