The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked toCD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells
recognized three breast cancer (BC) and one colon cancer cell line
among 15 tested in the absence of targeting antibodies. Sensitive
BC cell conjugation with CD32-CR T cells induced CD32 polarization
and down-regulation, CD107a release, mutual elimination,
and proinflammatory cytokine production unaffected by human
IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient
mice from subcutaneous growth of MDA-MB-468
BC cells. RNAseq analysis identified a 42 gene fingerprint predicting
BC cell sensitivity and favorable outcomes in advanced BC.
ICAM1 was a major regulator of CD32-CR T cell–mediated cytotoxicity.
CD32-CR T cells may help identify cell surface CD32 ligand(s)
and novel prognostically relevant transcriptomic signatures and
develop innovative BC treatments
