IN8bio Announces New Preclinical Data for Gamma-Delta nsCAR-T Cell Therapy Platform at AACR 2024 - Seite 2

The new data presented at AACR included results from proprietary constructs targeting CD33 and/or CD123 for in vitro evaluation against various types of leukemia, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The study results demonstrated notable differences between cells expressing traditional signaling CARs and those expressing the nsCAR constructs, which include a reduction in activation-induced cell death with nsCAR constructs.

The nsIL3-33mb15 CAR (CD123+CD33+IL-15) enhancement of the gamma delta T cells against leukemia cells demonstrated an average 1.8x increase in tumor killing capability across three AML cell lines (HL-60, KG-1a and MOLM-13), compared to unmodified gamma-delta T cells as measured by a 24-hour cytotoxicity assay. Importantly, the nsCAR cells did not lead to significant killing of healthy cells expressing the CD33 or CD123 target, demonstrating the selectivity of the nsCAR platform. Results were run in triplicate and on average the selectivity was increased by 5.5x. Across all runs, killing by the nsIL3-33mb15 construct against healthy CD34+ HPCs was below that of un-transduced control gamma-delta T cells.

“INB-300 can selectively target leukemia cells while preserving healthy tissue. We are now conducting further optimization to improve the integration of membrane-bound IL-15 co-expression to potentially enhance both the efficacy and safety of next-generation adoptive cell therapies against a wider spectrum of cancers,” said Lawrence Lamb, Ph.D., co-founder and Chief Scientific Officer of IN8bio. “These results can potentially improve INB-300, as we advance towards IND enabling studies of our next-generation gamma-delta T cell therapies to treat cancers.”

About INB-300

INB-300 is an nsCAR gamma-delta T cell platform with several preclinical product candidates, including the INB-330 program against AML targets, that combine our expertise in gamma-delta T cells and genetic engineering. These nsCAR constructs lack signaling domains in order to take advantage of the unique properties of gamma-delta T cells to differentiate between healthy and tumor tissues. IN8bio is advancing new nsCAR constructs against multiple targets to treat both solid and liquid tumors.