Immune effector cell antigen

Immune effector cell antigen is a functional designation for a group of cell surface proteins expressed on immune effector cells, such as T lymphocytes and natural killer (NK) cells, that serve as the recruitment arm for immunotherapeutic agents [1, 2, 3]. The most widely utilized immune effector cell antigen is the CD3 complex (specifically the CD3ε subunit) on T cells, which is targeted by bispecific T-cell engagers (BiTEs) and other multispecific antibodies to redirect T-cell cytotoxicity toward tumor cells [5, 13, 15]. Other examples include CD16 (FcγRIII) on NK cells, CD28 on T cells, and CD64 on myeloid cells [6, 7, 10]. By binding to these antigens, therapeutic molecules can bypass the requirement for traditional major histocompatibility complex (MHC) recognition, allowing for the potent activation of a broad population of effector cells against a specific target [3, 15]. While highly effective in treating various hematological malignancies, therapies targeting these antigens are often associated with significant systemic inflammatory side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) [10, 15].

Other names

Effector cell antigenImmune cell engager targetT-cell recruitment antigenNK-cell recruitment antigenEffector antigen

Immune effector cell antigens serve as the recruitment arm for multispecific antibodies or engagers. These drugs simultaneously bind a tumor-associated antigen (TAA) and an immune effector cell antigen (most commonly CD3 on T cells or CD16 on NK cells), thereby bringing the effector cell into close proximity with the target cell and triggering effector cell activation and directed lysis of the target cell [2, 3, 10].