ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

IFNβ is a potent adjuvant for cancer vaccination strategies (#105)

Katherine Audsley 1 , Teagan Wagner 2 , Clara Ta 1 , Hannah Newnes 1 , Anthony Buzzai 1 , Samantha Barnes 1 , Bree Foley 1 , Jason Waithman 1
  1. Telethon Kids Institute, Nedlands, WA, Australia
  2. The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

Cancer immunotherapies harnessing T cell immunity have shown remarkable clinical success in recent years. However, further advances are necessary for all patients to benefit. One caveat of current immunotherapy strategies is the reliance on pre-existing anti-tumour immunity. Cancer vaccination can overcome this by driving the generation of de novo tumour-specific T cells, yet there has been limited clinical efficacy with these strategies thus far. There is an unmet need for the discovery of novel, effective adjuvants that boost immune responses to cancer vaccination. We systematically compared the capacity of distinct type I interferon (IFN) subtypes to enhance T cell responses to a whole-cell vaccination strategy in a pre-clinical murine model. We identified that several type I IFN subtypes demonstrate significantly higher expansion of tumour-specific CD8+ T cells post-vaccination than vaccination alone, or with a gold standard adjuvant, poly I:C. Furthermore, expanded tumour-specific CD8+ T cells were shown to successfully infiltrate into the tumour microenvironment. Importantly, not all type I IFN subtypes were equal, with IFNβ proving to be a superior adjuvant. Optimal expansion was dependent on the presence of XCR1+ dendritic cells, CD4+T cells, and CD40/CD40L signalling. Therapeutically, vaccination with IFNβ delayed tumour progression and synergized with anti-PD-L1 checkpoint blockade therapy (CPB) to further promote overall survival. This work demonstrates the potent adjuvant activity of IFNβ, highlighting its potential to enhance cancer vaccination strategies alone and in combination with CPB.