Harnessing the body's immune system to fight cancer

Recently approved cancer immunotherapies have caused a paradigm shift in the treatment of clinically-advanced cancers. The most prominent and successful approach to date - checkpoint inhibitors - work by releasing the brakes off the immune system, thereby allowing pre-existing immune responses (specifically CD8 T cell responses) to infiltrate tumors and kill cancer cells. However, despite their success, checkpoint inhibitors are only partially effective in many patients because these patients do not have adequate pre-existing T cell responses against their tumors.

Neoantigen vaccination - revealing the hidden targets

The genetic instability of cancer leads to the generation of mutant proteins, referred to as neoantigens, that appear foreign to the immune system. As neoantigens are present only in cancer cells and are unique to each individual, neoantigens represent a highly specific and individualized target for focusing the immune system to kill cancer cells. However, as most patients have little or no pre-existing immune response against their tumor neoantigens, vaccines must be deployed to generate de novo T cell responses. Avidea is developing individualized vaccines that offer a safe and potent approach to generating neoantigen-specific T cell responses.

An individualized approach to cancer treatment

Advances in DNA and RNA sequencing technologies and in silico predictions are making it possible to rapidly identify the neoantigens present in patient tumor samples. These neoantigens can then be targeted by vaccines to generate neoantigen-specific T cell responses, however, most current vaccine technologies are either inadequately potent to promote tumor clearance or are not sufficiently generalizable to work for all patients. Avidea's nano-scaffold addresses both challenges by providing:

1. Increased potency. Current approaches of mixing peptide-based neoantigens with immuno-stimulants induces low level responses against a limited number of neoantigens. Our approach of delivering immuno-stimulants and neoantigens together on self-assembling nano-particles has been shown to provide a higher magnitude and breadth of T cell responses that together promotes improved tumor clearance.

2. Improved generalizability. The genetic diversity of tumors means that each patient has a unique set of neoantigens with varying physical and chemical properties. Current approaches largely do not account for these differences in neoantigen properties, and this has led to variable and unpredictable immune responses to neoantigen vaccines. To address this problem, Avidea has developed a self-assembling technology that allows for any patient neoantigen to be optimally delivered on our nano-scaffold platform (independent of the underlying properties of the peptide), thereby providing a generalizable, controlled, and chemically-defined approach to individualized neoantigen vaccines.