755P B7H3-targeted tri-specific killer engagers deliver IL-15 to NK cells but not T-cells, and specifically target solid tumors as a pan-tumor antigen strategy mediated through NK cells

Abstract

IL-15, the homeostatic factor for NK cells is being clinically developed but it has little antitumor activity alone. We hypothesized that targeted delivery of IL-15 to NK cells along with ADCC would impart NK cells with specificity to tumor antigens. As proof of concept, a clinical trial of GTB-3550 (a CD33-targeted Tri-specific Killer Engager [TriKE] in AML) induced endogenous NK cell expansion and activation in refractory AML patients. Here we developed GTB-5550 (a B7H3 TriKE) as a novel dual camelid (cam) TriKE containing WT IL-15 and comprised of two cam engagers: targeting CD16 on NK cells and B7H3 on multiple solid tumors.