BCMA (tumor cells) x CD3 (T cells), plus serum albumin binding for

Class

Tri-specific T-cell activating construct (TriTAC)

Pathway

Trispecific protein (originally Harpoon Therapeutics' HPN217, licensed to Merck as MK-4002) that bridges BCMA-expressing myeloma cells to CD3+ T cells to drive T-cell-mediated cytotoxicity

Notes

original target text: BCMA (tumor cells) x CD3 (T cells), plus serum albumin binding for half-life extension

This mechanism belongs to a class of engineered proteins designed to redirect the immune system against multiple myeloma, a cancer of antibody-producing plasma cells. BCMA (B-cell maturation antigen) is a surface receptor found almost exclusively on mature B cells and, more heavily, on malignant plasma cells, making it an attractive tumor marker. CD3 is a signaling component of the T-cell receptor complex present on essentially all T cells. The construct described here is a trispecific protein containing three binding arms: one recognizes BCMA on tumor cells, a second recognizes CD3 on T cells, and a third binds serum albumin, an abundant blood protein. By simultaneously gripping both cell types, the molecule physically bridges a T cell to a tumor cell, forcing formation of an immune synapse that triggers the T cell to release cytotoxic granules and kill the tumor cell, independent of the T cell's normal antigen-recognition machinery. The albumin-binding arm does not contribute to killing directly; it extends the molecule's residence time in circulation, since small engineered proteins are otherwise cleared rapidly by the kidneys. This general approach, T-cell engagement against BCMA, is broadly relevant across plasma cell malignancies and reflects a wider strategy of using bispecific or multispecific proteins to recruit a patient's own T cells against tumors that evade conventional immune surveillance.