Pathogen-Boosted Adoptive Cell Transfer Therapy Induces Endogenous Antitumor Immunity through Antigen Spreading.

ABSTRACT: Loss of target antigens in tumor cells has become one of the major hurdles limiting the efficacy of adoptive cell therapy (ACT)-based immunotherapies. The optimal approach to overcome this challenge includes broadening the immune response from the initially targeted tumor-associated antigen (TAA) to other TAAs expressed in the tumor. To induce a more broadly targeted antitumor response, we utilized our previously developed Re-energized ACT (ReACT), which capitalizes on the synergistic effect of pathogen-based immunotherapy and ACT. In this study, we showed that ReACT induced a sufficient endogenous CD8⁺ T-cell response beyond the initial target to prevent the outgrowth of antigen loss variants in a B16-F10 melanoma model. Sequentially, selective depletion experiments revealed th

SUBMITTER: Xin G 

PROVIDER: S-EPMC6946848 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature