Antibody-coupled T-cell receptor (ACTR)

The Antibody-coupled T-cell receptor (ACTR) is an engineered chimeric receptor expressed on T cells that serves as a universal platform for cancer immunotherapy. Unlike traditional Chimeric Antigen Receptors (CARs) that are fixed to a single antigen, ACTR is designed to bind the Fc region of various monoclonal antibodies (mAbs) (Kudo et al., 2014, Scientific Reports). This modularity allows the same ACTR-T cell product to be redirected against different tumor antigens, such as CD20 or HER2, depending on the specific antibody co-administered (ClinicalTrials.gov, NCT03189836). Upon binding to the antibody-coated tumor cell, the ACTR initiates intracellular signaling through domains like CD3ζ and 4-1BB, leading to T-cell activation and potent anti-tumor cytotoxicity (D'Aloia et al., 2018, Frontiers in Immunology). This technology, developed by companies like Unum Therapeutics, aims to combine the specificity of established antibody therapies with the powerful effector functions of T cells. Clinical trials have explored ACTR in both hematologic malignancies and solid tumors, though safety monitoring for cytokine release syndrome remains a critical component of its therapeutic application (Cogent Biosciences, 2021).

Other names

Fc receptor-chimeric antigen receptorFcR-CARCD16-CARACTR087ACTR707Antibody-coupled T-cell receptor

The ACTR receptor is a chimeric protein that combines the extracellular domain of the CD16 (FcγRIIIa) receptor with intracellular T-cell signaling domains, such as CD3ζ and 4-1BB. It functions by binding to the Fc portion of a co-administered therapeutic monoclonal antibody, which in turn binds to a specific tumor-associated antigen. This tripartite interaction (T cell-antibody-tumor cell) creates an artificial immunological synapse that triggers T-cell activation, proliferation, and the release of cytotoxic granules to induce tumor cell lysis.