Adaptive T-Cell Therapies for the Treatment of Lymphoma
2020 VCS Virtual Conference
Nicola Mason

T cells that exhibit specificity towards tumor associated antigens represent a powerful natural tool that can be manipulated to enhance their therapeutic effects against both solid and hematological malignancies. Frequently, these manipulations occur ex vivo and involve expanding either peripheral T cells or those extracted from the tumor itself (tumor infiltrating lymphocytes or TILs) to generate large numbers of tumor specific T cells that are then adoptively transferred back into the patient. Several strategies have been employed to increase the percentage of tumor-specific T cells prior to ex vivo expansion. These include vaccination of the patient prior to T cell harvest and genetic modification of T cells to express a synthetic T cell receptor or chimeric antigen receptor (CAR) specific for the tumor antigen of interest after T cell harvest. Both methodologies are currently being tested in clinical trials in the veterinary clinics. In the human arena, perhaps the most remarkable clinical results to date have been achieved using autologous CAR-T cells in patients with hematological malignancies such as acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (B-CLL), B-non Hodgkin lymphoma (B-NHL) and multiple myeloma (MM). In dramatic fashion, adoptively transferred CAR-T cells have been shown to rapidly and effectively eliminate kilograms of tumor and provide durable remissions that correlate with long-term persistence of these cells. Next-generation CAR-T strategies are now focused on developing allogeneic, off-the-shelf products that can function within the immunosuppressive microenvironment, which aims to improve CAR-T effectiveness in solid tumors. The tools and protocols to generate autologous and allogeneic tumor-specific T cells are now available in the veterinary field and clinical trials are underway to assess their safety and efficacy in dogs with B cell lymphoma. In this lecture we will explore the current use and up-coming strategies to improve upon current adoptive T cell therapies in dogs with B cell lymphoma, outlining how the field is moving towards obtaining durable clinical responses in dogs with this challenging disease.

 

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Nicola Mason


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