Session: 702. CAR-T Cell Therapies: Basic and Translational: Poster III
Hematology Disease Topics & Pathways:
Research, Translational Research
In vitro cytotoxicity assays following co-incubation of CD276-positive NOMO-1 cells and CD276 negative Kasumi-1 cells with either CD276 CAR T or unmodified T cells showed robust target specific cell killing across a variety of effector: target cell ratios in the NOMO-1 cells with no significant cytotoxicity in the CD276-negative Kasumi-1 cells (p<0.0001). Cytokine production assessed via Human Luminex Assay with supernatant collection following 24hr co-incubation at a 1:1 effector to target ratio in a CD276-positive cell line revealed proinflammatory cytokine production in the CD276 CAR T treated co-cultures to be 100-300 fold higher than in the unmodified T cell treated co-cultures, demonstrating significant reactivity of the CD276 CAR T cells (p<0.001) with negligible cytokine production in the antigen negative cell line.
In vivo evaluations of the CD276 CAR T cells were conducted in an aggressive KMT2A-r AML cell-derived xenograft model. NSG mice were transplanted with 1e6 ffLuciferase transduced NOMO-1 cells and allowed 1 week for leukemia engraftment. Mice were then treated with 3.5e6 unmodified T cells or CD276 CAR T cells and leukemic burden was monitored by weekly bioluminescent imaging and flow cytometry analysis of peripheral blood. All CAR T-cell treated mice showed dramatic disease reduction as indicated by a significant reduction in radiance (>1 log fold decrease) within 6 days of CAR T cell infusion and clearance of disease maintained through the duration of the experiment. In contrast, all control animals who received unmodified T cells had progressive disease evidenced by >2 log fold increase in radiance.
We demonstrated potent and target specific efficacy of CD276 CAR T in an aggressive model of AML. As a tumor-specific antigen, CD276 represents an ideal therapeutic target in a very high-risk cohort of AML. This CAR T is advancing into clinical development pending completion of ongoing IND enabling studies.
Disclosures: Barisa: University College London: Patents & Royalties: B7H3 CAR T. Pardo: Hematologics: Current Employment. Loken: Hematologics: Current Employment.
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