DIFFERENTIAL EFFECTS OF IMMUNOSUPPRESSANTS ON THE FUNCTION OF ENGINEERED TCR-T CELLS

Abstract

Background: mRNA-engineered T cell immunotherapy has shown potential therapeutic effects in HBV-related HCC relapsed patients who have previously undergone curative liver transplantation. Such patients received various immunosuppressive regimen including Tacrolimus with/without adjunctive MMF or Rapamycin following liver transplantation, which can affect the efficiency of our TCR-T therapy. Objective: The objective of this study is to assess the impact of clinically relevant immunosuppressants on the function of TCR-redirected T cells. Methods: T cell’s function were monitored in the presence and absence of various immunosuppressants using 2D and 3D culture systems. Results: short term exposure to Tacrolimus alone or in combination with MMF severely impact infiltration, cytokine production and cytolysis of engineered TCR-T cells. In contrast, Rapamycin treatment did not suppress cytolysis and cytokine production, but could reduce T cell infiltration. This finding has important clinical implication in the selection of immunosuppressive agents used in conjunction with TCR-T Immunotherapy.