Anti-Human CD3 x BCMA (Teclistamab) [Clone JNJ-64007957] — Fc Muted™,Leinco,C975

CD3 is an invariant antigen of the T cell TCR (T cell receptor) 1 . BCMA is a member of the tumor necrosis factor family of receptors that regulates B cell maturation, proliferation, and survival by activating p38/NF-κB and inducing upregulation of antiapoptotic proteins 2 . BCMA is highly expressed on multiple myeloma (MM) cells and is therefore a target of cancer immunotherapy. Teclistamab is a humanized IgG4-proline, alanine, alanine (IgG4-PAA) DuoBody CD3xBCMA Bispecific T cell Engager (BiTE) antibody developed for treatment of MM 2,3 . Teclistamab treatment redirects CD3+ T cells to BCMA-expressing MM cells, leading to the secretion of perforin and certain granzymes from the cytotoxic T cells and ultimately inducing antibody-dependent cell cytotoxicity and tumor cell death of the BCMA-expressing B cells. The process is not specific and MHC I molecules on antigen presenting cells are not involved 3 . Teclistamab treatment also leads to the secretion of interferon-γ, TNF-α, IL-2, IL-6, IL-8, and IL-10 2 cytokines are induced 2,3 . Additionally, activity is increased by the γ-secretase inhibitor LY-411575 2 . Teclistamab was generated by immunizing OmniRats (Open Monoclonal Technology) with BCMA-Fc recombinant protein and re-cloning hits on a relatively silent IgG4-PAA scaffold 2 . A controlled Fab-arm exchange of a BCMA antibody and a CD3 parental antibody derived from SP34 was then performed. The Fc region of Teclistamab contains S228P/L234A/L235A mutations to minimize its immunological effector functions. Teclistamab has been approved for treatment of MM in patients who demonstrate disease progression despite treatment 3 .