gamma delta CAR T cells with alternative CD3 cytoplasmic domains

Gamma delta (γδ) CAR T cells with alternative CD3 cytoplasmic domains are an experimental cellular immunotherapy designed to enhance the activation and cytotoxicity of γδ T cells against cancer. While traditional CAR constructs utilize the CD3ζ (zeta) signaling domain, this approach incorporates alternative CD3 subunits—specifically CD3δ (delta), CD3ε (epsilon), or CD3γ (gamma)—into the CAR's intracellular signaling tail. γδ T cells are attractive for therapy due to their MHC-independent antigen recognition and low risk of graft-versus-host disease (GvHD), making them suitable for allogeneic "off-the-shelf" applications. Research presented at AACR 2026 indicates that these alternative domains can outperform conventional CD3ζ-based CARs in terms of effector function and antitumor efficacy in preclinical models, such as the NALM-6 leukemia xenograft.

Other names

γδ CAR T cells with alternative CD3 subunitsCD3δ/ε/γ-based γδ CAR T cells