On February 23, 2023 IN8bio, a clinical-stage biopharmaceutical company discovering and developing innovative gamma-delta T cell therapies, reported the ability of its novel non-signaling gamma-delta CAR-T platform (nsCAR) to selectively target leukemic cells while preserving healthy B cells (Press release, In8bio, FEB 23, 2023, View Source [SID1234627612]). The findings were presented by Dr. Lawrence Lamb, IN8bio’s Chief Scientific Officer, during a Plenary session titled "Leveraging the Nexus of the Immune System with Gamma-Delta CAR-T Cells" at the 6th CAR-TCR Summit Europe on February 23rd.
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The current generation of CAR-T technology eliminates the target antigen regardless of whether it is expressed on tumor or healthy tissues. However, IN8bio’s nsCAR platform uses the innate immune recognition of gamma-delta T cells to distinguish between tumor and healthy tissue, offering a targeted but potentially less toxic approach. In a 48-hour in vitro cytotoxicity experiment, the nsCAR platform demonstrated a greater than 15x difference in killing between leukemic cells and healthy B cells (E:T=2:1, 79.7% versus 5.2%) when both express the CD19 target antigen.
The nsCAR platform is also engineered to express the cytokine interleukin-15 (IL-15) to enhance cellular persistence and the ability to target and kill tumor cells over time. The platform has the potential to broaden the utilization of CAR technology for previously "undruggable" solid and liquid tumor targets.
"This powerful approach could be used in indications such as acute myeloid leukemia (AML) and solid tumor cancers where on-target, off-tumor expression would result in toxicities with significant risks to patients," said Lawrence Lamb, Ph.D., co-founder and Chief Scientific Officer of IN8bio. "While CD19 was a preclinical proof-of-concept, we look forward to advancing the nsCAR platform into solid tumor indications as well as promising targets for AML, such as CD33."
The data presented supports the potential of IN8bio’s nsCAR platform to revolutionize the development of future CAR-T therapies, with the findings demonstrating the ability of the novel approach to distinguish between tumor cells and healthy tissue. The presentation is available on the company’s website at View Source
About INB-300
INB-300, our non-signaling CAR gamma-delta T cell platform, includes several preclinical product candidates combining 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.