THE OPTIMIZATION OF THERAPEUTIC CANCER VACCINES
Taylor, David Raynard
0000-0002-5381-9963
:
2022-11-17
Abstract
The emergence of immunotherapy as a new pillar of cancer treatment is due to the success of immune checkpoint blockade drugs. However, many patients receiving checkpoint blockade fail to respond, and consensus evidence shows high T-cell infiltration in the tumor microenvironment positively correlates with clinical response to checkpoint blockade. Cancer vaccines have been previously shown to boost T-cell infiltration and, therefore, a viable option to combine with cancer vaccines. Cancer vaccines have two components: an antigen source which provides specific targets for the immune system to react to, and the adjuvant, which boosts the immune response to those targets. However, cancer vaccines have failed clinical trials due to a lack of clinical efficacy. Here, we modified the two components to maximize cancer vaccines' T-cell priming and antitumor capacity. We performed in vitro and in vivo assays assessing the immunogenicity and antitumor response. Overall, we show that modifying the antigen source and adjuvant led to various T-cell priming responses but ultimately increased antitumor efficacy. This work will pave the way for a more rigorous approach to identifying combinations for checkpoint blockade therapies.