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. Public Health Relevance Statement PROJECT NARRATIVE Project Title: Engineered TCR-T Cell Therapies Targeting Shared Tumor Associated Antigens Organization: GigaMune Inc. PI: Matthew J Spindler, Ph.D. Cancer remains an intractable disease, but doctors have been achieving incredible results with new therapies that rely on genetic engineering of T cells. We are using microfluidics and DNA sequencing to capture disease- modulating T cells from patients. Antitumor genes from these T cells are then engineered into healthy T cells to create a TCR-engineered T cell therapy.
Project Terms: Alleles ; Allelomorphs ; Epitopes ; Antigenic Determinants ; Binding Determinants ; Antigens ; immunogen ; Differentiation Antigens ; Differentation Markers ; Differentiation Markers ; Marker Antigens ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biotechnology ; Biotech ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Cells ; Cell Body ; Clinical Research ; Clinical Study ; Clinical Trials ; Disease ; Disorder ; Engineering ; Genes ; Genetic Engineering ; Genetic Engineering Biotechnology ; Genetic Engineering Molecular Biology ; Recombinant DNA Technology ; genetically engineered ; HLA Antigens ; HL-A Antigens ; Human Leukocyte Antigens ; Leukocyte Antigens ; Human ; Modern Man ; In Vitro ; Libraries ; melanoma ; Malignant Melanoma ; Patients ; Peptides ; Publishing ; Relapse ; synovial sarcoma ; Synovioma ; synovial cell sarcoma ; T-Lymphocyte ; T-Cells ; thymus derived lymphocyte ; Technology ; Testing ; Testis ; Testicles ; Tumor Antigens ; Tumor-Associated Antigen ; cancer antigens ; tumor-specific antigen ; Tumor-Infiltrating Lymphocytes ; improved ; Clinical ; Refractory ; Phase ; Solid Neoplasm ; Solid Tumor ; tumor infiltrating lymphocyte therapy ; TIL therapy ; Tumor Escape ; Tumor Immune Escape ; cancer evasion ; cancer immune escape ; cancer immune evasion ; tumor evasion ; tumor immune evasion ; Nature ; adoptive cell therapy ; adoptive cellular therapy ; Adoptive Cell Transfers ; Hematologic Cancer ; Hematologic Malignancies ; Hematological Malignancies ; Hematological Neoplasms ; Hematological Tumor ; Hematopoietic Cancer ; Malignant Hematologic Neoplasm ; Hematologic Neoplasms ; catalog ; Catalogs ; Autologous ; Protocol ; Protocols documentation ; interest ; cell killing ; novel ; response ; Genomics ; antigen bound ; antigen binding ; µfluidic ; Microfluidics ; Common Tumor ; Common Neoplasm ; CD19 ; CD19 gene ; CTAG ; CTAG1 ; CTAG1B ; CTAG1B Gene ; ESO1 ; LAGE2B ; NY-ESO-1 ; CTAG1 gene ; Address ; Avidity ; Ph.D. ; PhD ; Doctor of Philosophy ; in vivo ; Allogenic ; Antigen Targeting ; Cancer Patient ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Development ; developmental ; safety study ; clinical efficacy ; Population ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; tumor ; high risk ; FDA approved ; patient population ; treatment response ; response to treatment ; therapeutic response ; effective therapy ; effective treatment ; T cell response ; T cell therapy ; T cell based therapeutics ; T cell based therapy ; T cell targeted therapeutics ; adoptive T cell transfer ; adoptive T-cell therapy ; therapeutic T-cell platform ; targeted treatment ; targeted drug therapy ; targeted drug treatments ; targeted therapeutic ; targeted therapeutic agents ; targeted therapy ; efficacy study ; DNA sequencing ; DNA seq ; DNAseq ; anti-tumor immune response ; antitumor immune response ; Epitope spreading ; antigen spreading ; Immunogenomics ; anti-cancer ; anticancer ; engineered T cells ; chimeric antigen receptor T cells ; CAR T cells ; T cells for CAR ; chimeric antigen receptor (CAR) T cells ; CAR T cell therapy ; CAR T therapy ; chimeric antigen receptor (CAR) T cell therapy ; chimeric antigen receptor T cell therapy ;
