Constructing artificial antigen-presenting cells for improved T-cell function in adoptive T-cell therapy of melanoma

PhD student: Christina Friese, M.Sc.

​Adoptive T-cell therapy (ACT) is a cancer immunotherapy for metastatic melanoma patients based on autologous tumor-infiltrating lymphocytes (TILs). TIL therapy takes advantage of naturally existing tumor-reactive T cells already present within the tumor which are isolated from surgically resected tumor lesions, expanded ex vivo and re-infused into the patient after lymphodepleting chemotherapy and in combination with recombinant IL-2. With this personalized therapy objective response rates of up to 50% including complete tumor regression in 10-20% of the patients have been reported from several independent centers.
Despite the great potential TIL therapy has shown in the treatment of metastatic melanoma, some confounding issues are still to be addressed prior to entry into the standard of care for melanoma patients. An important area requiring improvement is the technical protocols for expansion of TILs for therapy. At present, a large number of peripheral blood mononuclear cells (PBMCs) derived from different blood donors is required to be used as feeders/stimulators for the rapid-expansion protocol (REP).
Genetically engineered artificial antigen-presenting cells (aAPCs) that express any desired T-cell activating or co-stimulatory molecule on the cell surface have the potential to eliminate the need to use PBMCs from multiple donors and could lead to improved effector-memory qualities with a longer persistence of TILs in the patients.
The aAPCs currently being established at CCIT are genetically modified with various T-cell co-stimulatory molecules and Fc receptors for antibody loading. In this project the aAPCs' feasibility in expanding TILs for ACT of melanoma as well as renal cancer, ovarian cancer and sarcoma is tested.​