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Logic-gated CAR-T

Courtesy of Ronald Korn, M.D. Ph.D., Imaging Endpoints Core Lab

Logic gate-controlled CAR-T technology

Chimeric Antigen Receptor (CAR)-T cell therapy has delivered remarkable on-target responses to certain hematological malignancies. However, in solid tumors, on-target, off-tumor toxicity has limited the number of antigens available for potent targeting by CAR-T technology. Our logic-gate technology takes advantage of the unique microenvironment associated with different diseases and tissues, such as solid tumors, which can result from differences in metabolism between diseased and normal tissue. Our logic-gated CAR-Ts require both the target antigen AND the tumor microenvironment (TME) to become fully activated and will therefore only work in tumor—not normal—tissue, thereby reducing potential on-target, off-tumor toxicity.

Our solution for CAR-T tumor precision

EXUMA’s CAR-T cells display “AND logic-gate” properties, requiring both target antigen and tumor microenvironment (TME) for activity

  • Our “logic-gated” technology leverages the unique nature of the acidic TME (the result of Warburg effect) as an activating signal to activate the CAR-T cells when they are near the tumor
  • In this manner, even if there is antigen present on normal tissue, the CAR-T cells remain off when not near the tumor
  • The process is also reversible so that when CAR-T cells leave the TME, the will not react with normal tissue expressing a target antigen
  • This means that a broader range of target antigens are available in targeting the tumor: Based on EXUMA’s internal bioinformatics models, up to 90% of solid tumors could be targeted with only 10 logic-gated CAR-T constructs