Technology

Genocea's T Cell Antigen Discovery Technology: AnTigen Lead Acquisition System (ATLAS™)

Genocea's vaccine development programs are built around a transformational platform for the rapid discovery of T cell antigens. T cell antigens, specifically antigens that stimulate CD4⁺ and CD8⁺ T cells, are critical to generating disease-specific cellular immune responses and long-term T cell memory.

To date, T cell antigen discovery has proven a significant barrier to vaccine development. While several advances have been made in antigen delivery methods, relatively few have been made in developing strategies to identify protective T cell antigens that can be incorporated into vaccine formulations. The company's approach addresses several key challenges to antigen discovery, including: identification of promising antigens from among the thousands of possible candidates for each pathogen and selection of antigens with potential to provide protection across diverse populations.

In less than three years, Genocea has taken four programs in three diseases from project initiation to animal proof-of-concept, a dramatically accelerated pace compared with up to 10-12 years with traditional discovery approaches. The technology is based on pioneering research from the University of California at Berkeley and Harvard Medical School.

High Throughput Approach Mimics Natural Immune Response

At the core of Genocea's antigen discovery technology (illustrated above) is a high throughput screening process that mimics the natural mammalian immune response to protein antigens, including antigen processing and presentation by antigen presenting cells (APCs); CD4⁺ and CD8⁺ T cell recognition of APC-displayed peptides; and immune activation. Critically, the company screens all of a pathogen's proteins against T cells obtained from human donors with diverse HLA types who have either generated a potentially protective or ineffective immune response after exposure to a target pathogen. As part of its discovery approach the company creates a library of each pathogen's complete proteome.

As a result, through Genocea's discovery process the 2000-3000 proteins produced by a pathogen are rapidly winnowed down to a set of 100-200 protein antigens that correlate with natural immunity. A subset of proteins from that group is selected for in vivo testing, based on recognition across multiple HLA supertypes and other criteria, with the goal of identifying two to five antigens for formulation and development into a vaccine candidate that will be protective across diverse ethnic populations.