Anti-GD2 Virus-Free CRISPR CAR T cells to treat canine sarcomas
Chimeric Antigen Receptor T (CAR-T) cell therapies have had limited success in treating solid tumors. Our lab has developed a novel virus-free strategy to engineer T cells that uses CRISPR-Cas9 to precisely insert a CAR targeting the antigen disialoganglioside (GD2) into the TRAC gene encoding for the existing T cell receptor (TCR). GD2 is over-expressed in many solid tumor types in humans and dogs, and has limited expression in healthy tissues, making it an ideal target for solid tumor immunotherapy. Virus-free CRISPR (VFC) CAR T cells have a favorable memory-like phenotype and show fewer exhaustion markers than CAR T cells manufactured using viral vectors. However, the safety and long-term efficacy of this treatment in immunocompetent hosts is unclear. The aim of my research is to manufacture and introduce VFC canine anti-GD2 CAR T cells into a companion canine cancer patient population to develop a potential treatment for GD2+ solid tumors. The knowledge gained through these studies are likely to inform immunotherapy strategies for both canine and human patients and provide insight on VFC CAR efficacy in an immunologically competent parallel patient population.