FT536 + cetuximab

FT536 + cetuximab is an investigational combination therapy for solid tumors, comprised of FT536, an off-the-shelf, induced pluripotent stem cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell product engineered to target the α3 domain of MICA and MICB stress proteins, in conjunction with cetuximab, an anti-EGFR monoclonal antibody. FT536 incorporates four engineered elements: a 3MICA/B CAR for direct tumor targeting, a high-affinity, non-cleavable CD16 Fc receptor (hnCD16) to enhance antibody-dependent cellular cytotoxicity (ADCC), an IL-15 receptor fusion (IL-15RF) to augment NK cell activity and persistence, and CD38 knockout to improve function in oxidative environments. The combination is designed to leverage direct tumor cell lysis by CAR-NK cells and ADCC mediated by cetuximab bound to EGFR-expressing tumor cells, overcoming tumor heterogeneity and antigen escape. Fate Therapeutics is developing this combination for the treatment of advanced, refractory, or recurrent solid tumors, with early clinical evaluation in Phase 1 trials for cancers such as non-small cell lung, colorectal, head and neck, gastric, breast, ovarian, and pancreatic cancer[1][2][5][7].