Preconditioning before CarT Therapy

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AVM0703 dramatically improves the effectiveness of car-t cells in a melanoma model

AVM0703 also delayed melanoma tumor growth equivalently to 20M pmel CarT cells (female donor) and, used as a preconditioning agent, significantly improved melanoma response to pmel CarT cells. Higher AVM0703 doses were equivalent to Cy preconditioning in the Mouse B16F10 Melanoma Model when CarT pmel cells from male donor mice were used.

B16F10 melanoma cells are inoculated on day -9.  Pre-conditioning is done on day 1 with low dose AVM0703 or on day 2 with 13 mg /kg HED Cyclophosphamide.  Adoptive transfer of 20M transgenic CD8+ cells expressing the anti-gp100 TCR from pmel-1 mice is done on day 3.  Tumor volumes are measured by calipers.  A single dose of AVM0703 is as effective as 20M pmel cells to delay tumor growth.  AVM0703 and Cy pre-conditioning before 20M pmel cells both significantly delay tumor growth compared to 20M pmel cells alone and compared to their use alone.