A universal CAR-T cell platform based on the P329G mutation in therapeutic IgG1 antibodies

• Development of universal CAR-T cells that engage with adaptor molecules possessing the P329G mutation, that is clinically used to silence the Fc effector function of therapeutic antibodies
• Selective recruitment of P329G CAR-T cells in the presence of the respective P329G-containing IgG1and potent tumor cell lysis was demonstrated for multiple tumor antigens e.g. CD20, HER2, FOLR1, EpCAM, MSLN and FAP
• For all tested antigens, a huIgG1 dose-dependent activation of anti-P329G-CAR-T cells as well as dose-dependent tumor cell lysis was observed.
• The P329G-CAR-T cells might help to overcome existing limitations of direct CAR T cells like engaging multiple tumor targets and regulation of CAR-T potency

Diana Darowski, Scientist, Cancer Immunotherapy Department, Roche Innovation Center Zurich