Recombinant TIL Cell Therapy for Salvage Solid Tumor Patients

PROJECT SUMMARY Project TitleRecombinant TIL Cell Therapy for Salvage Solid Tumor Patients OrganizationGigaMune IncPIMatthew J SpindlerPh DExpanded T cells isolated from tumor infiltrating lymphocytesTILshave achieved remarkable clinical efficacy for the treatment of metastatic melanomaTILs are composed of a polyclonal mix of tumor reactive T cell receptorsTCRsand several pioneering groups have isolated individual therapeutic TCRs targeting public tumor associated antigens from TILsThe anti tumor TCRs within the TIL population are able to target the many intracellular and patient specific neoantigen targets not previously druggableHoweverex vivo expansion of TILs is labor intensivetime consumingand may result in cellular phenotypic changes that could reduce efficacyIsolating TCRs from pre expandedyoungTIL populations would alleviate these issues and could be converted into a recombinant anti tumor therapyLeaders in the field have proposed that primary T cells engineered with polyclonal anti tumor TCRs could be an ideal therapeutic approachHoweverconventional T cell discovery relies on low throughput methods and requires subsequent cloning of individual reactive TCRsGenerating a truerecombinant TILtherapy requires a technology that can capture millions of T cells per hour and produce polyclonal libraries of TIL TCRs with native TCRa b pairingPreviouslywe developed GigaLinka world leading technology for generating recombinant TCR repertoires from primary T cell samplesWe have used this technology to make expression libraries of natively paired TCRs from five clinically validated malignant melanoma TILsThe Specific Aim of this Phase I SBIR project is to generate pre clinical efficacy data in mouse models for a recombinant TIL T cell therapeutic approach for the personalized treatment of cancerWe will achieve the Specific Aim by applying our GigaLinktechnology to patient derived xenograftPDXtumor models in mice PROJECT NARRATIVE Project TitleRecombinant TIL Cell Therapy for Salvage Solid Tumor Patients OrganizationGigaMune IncPIMatthew J SpindlerPh DCancer remains an intractable diseasebut doctors have been achieving incredible results with new therapies that rely on genetic engineering of T cellsWe are using microfluidics and DNA sequencing to capture diseasemodulating T cells from patientsAnti tumor genes from these T cells are then engineered into healthy T cells to create a patient specific engineered T cell therapy