| Description |
Treatment of hematopoietic malignancies is challenging due to systemic side effects of current treatments and the possibility of relapse. Multi-antigen T cell hybridizer (MATCH) therapy is a novel treatment system composed of antibody fragments conjugated with morpholino oligonucleotides, which hybridize upon contact and direct autologous T cells against cancerous B cells. However, T cell exhaustion remains a challenging obstacle to the efficacy and duration of MATCH therapy. In this study, co-cultures of healthy human T cells and Raji B lymphoma cells were treated with MATCH therapy in vitro. Subsequent T cell activation, effector function, and exhaustion were assayed using immunohistochemistry and flow cytometry for corresponding cell surface markers. Interferon (IFN)-γ release was quantified using enzyme-linked immunosorbent assay. MATCH activation of T cells induced increases in PD-1 expression and IFN-γ release during the first 72 hours of co-culture and treatment. Multiple strategies aimed at reducing exhaustion and improving T cell ablation of lymphoma cells were then assessed. Ibrutinib pre-treatment of T cells moderately attenuated PD-1 expression but did not improve cancer cell clearance. Simultaneous administration of MATCH therapy with either PD-1 or IL-10 blockade reduced T cell PD-1 expression and markedly improved cancer cell clearance. These results suggest that immunomodulation, in the form of antibody blockades, has the potential to attenuate T cell exhaustion and enhance T cell effector functions during |
