Immune checkpoint inhibition enhances memory T-cell responses to CEF(T), SARS-CoV-2 spike proteins and ChAdOx1 nCoV-19

Abstract

ABSTRACT An extensive body of clinical and experimental evidence demonstrates that immune checkpoint blockade can invigorate recall immune responses. This phenomenon has previously been highlighted using ex vivo (healthy donor) and in vivo (immunotherapy patients) models of immune checkpoint inhibitor (ICI) administration that demonstrate an enhancement of the T-cell response to concomitant small-molecule drugs. However, the immunological and clinical impact of ICI therapy pre-ceding vaccination, where robust antigen-specific immunogenicity is essential, remains poorly defined. In this study, we utilized an ex vivo assay to evaluate lymphocyte recall responses within peripheral blood mononuclear cells (PBMC) derived from healthy donors and patients pre- and post-immunotherapy following exposure to SARS-CoV-2 derived peptides and ChAdOx1 nCoV-19. In line with the anticipated effects of the primary pharmacology of immune checkpoint inhibitors, we outline an acute increase in proliferation and cytokine and cytolytic molecule secretion following immune checkpoint blockade in response to CEF(T), wild-type SARS-CoV-2 spike pools 1 and 2, and ChAdOx1 nCoV-19. Future studies are needed to evaluate the clinical correlates of the veracity of such responses with protection and incidence of adverse events.