Importantly, STK-009 induced the expression of cytotoxic machinery, pro-survival, and proliferative genes in tumor-infiltrating SYNCAR-002 (figure 3). Conclusions These findings validate that the orthogonal IL-2 platform has the potential to improve the efficacy and durability of CAR T therapy for solid tumor targets such as GPC3 by selectively expanding CAR-T cells in vivo and activating CAR-T cells in a hostile tumor microenvironment.
Secondary endpoints include assessments of response, pharmacokinetics, and immunogenicity. Exploratory endpoints include assessment of immune cell populations, and relevant gene/protein expression, as well as persistence, phenotype, and functionality of SYNCAR-001 in the peripheral blood and/or bone marrow in response to STK-009.
STK-009 treatment resulted in significant expansion of SYNCAR-002 and drove infiltration of SYNCAR-002 into tumors. STK-009 treatment also induced intratumoral granzyme B+ and IFN-γ+ production by SYNCAR-002 indicating activation of effector T cell function.These findings validate that the orthogonal IL-2 platform has the potential to improve the efficacy and durability of CAR T therapy for solid tumor targets such as GPC3 by selectively expanding CAR-T cells in vivo, driving CAR-T cells into the tumor, and activating CAR-T cells in the tumor microenvironment.
Pharmacokinetic analysis of STK-009 shows stable exposure with minimal clearance, demonstrating the selectivity of STK-009.These findings validate an orthogonal platform that selectively drives potent T cell effector functions of engineered cells without the toxicities mediated by NK cells or non-tumor specific T cells associated with high dose IL-2 therapy. These results demonstrate the ability of this orthogonal platform to improve the efficacy and durability of CARs.