Engineered TCR-T Cell Therapies Targeting Shared Tumor Associated Antigens

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PROJECT SUMMARY Project Title: Engineered TCR-T Cell Therapies Targeting Shared Tumor Associated Antigens Organization: GigaMune Inc. PI: Matthew J Spindler, Ph.D. Adoptive cell therapies (ACTs) including CAR-T, TCR-T, and TIL therapies have shown strong clinical responses for the treatment of cancer patients for hematological cancers and solid tumors. However, only anti-CD19 CAR- T cell therapies have been FDA approved and commercialized for the treatment of hematological cancers. Numerous TCR-T cell clinical trials are ongoing for the treatment of solid tumors, but these trials target only a handful of tumor associated antigens (TAAs) with the majority restricted to HLA-A0201. Thus, there is a need to develop novel anti-cancer TCR-T cell therapies for the treatment of a broader patient population. TAAs including cancer/testis and differentiation antigens are ideal TCR-T cell targets as they are shared across patients and solid tumor types and can induce T cell responses across numerous HLA alleles. Importantly, a recent clinical trial demonstrated that autologous anti-TAA T cells can provide strong anti-tumor efficacy in high- risk solid tumor patients. However, these autologous anti-TAA T cells require intensive ex vivo expansion and can result in variable anti-tumor reactivity. This suggests that TCR-T cell therapies targeting common TAAs would provide an effective treatment for solid tumor patients and improve manufacturing consistency and efficacy. The Specific Aim of this Phase I SBIR project is to develop a catalog of natural human TCRs that target shared tumor associated antigens for use in autologous or allogeneic TCR-T cells therapies. GigaMune's unique technology uses microfluidics, genomics, and mammalian display to generate millions-diverse, natively paired TCRab repertoire libraries. The TCRab libraries are immortal, enabling repeated experimentation with a panel of antigens. This will expedite discovery of rare anti-TAA TCRs. The project is led by Dr. Matthew J. Spindler, an expert in immunogenomics and inventor of the GigaMune technology and supported by serial entrepreneur and co-founder David Johnson (GigaGen). After completing this Phase I SBIR project, GigaMune will further develop promising TCRs as TCR-T cell therapies, through in vivo efficacy studies, in vitro safety studies, and manufacturing development.