Our Science

The T cell Revolution

The biotech industry is in the midst of a T cell revolution, with significant investment devoted to the discovery of therapies than can harness the power of the T cell.

Why do T cells matter?

T cells, a type of white blood cell in the body, are an important part of the immune system that protects us from infectious diseases and cancer by specifically attacking infected or cancerous cells. While most agree that T cells play a foundational role in immuno-oncology, we believe harnessing T cells is also important in the development of effective therapies in the infectious disease space.

These two therapeutic areas are united by the need to identify the right targets (antigens) to stimulate a T cell response.

To date, attempts to develop vaccines and immunotherapies that act via T cell responses have not focused on finding the right T cell antigens, but have typically paired known targets of B cell responses with an adjuvant to stimulate a broad, non-specific immune response. Unfortunately, these approaches have been largely unsuccessful, which we believe is because a T cell response must be directed to the right antigens to be effective.

The Challenge of Identifying T cell Antigens

While modern science has become expert at finding targets of B cell responses, identifying the right T cell antigens has proven to be much more challenging due, in part, to the large number of potential antigens and human genetic complexity.

  • Number of potential targets:  Antibodies created by B cells tend to work by connecting with select proteins on the surface of a pathogen or target cell. By contrast, there can be three or four orders of magnitude more targets of T cell responses, since those cells are able to be stimulated by nearly any peptide from any protein associated with the pathogen or target cell.
  • Human genetic diversity:  Antibodies generally demonstrate similar efficacy in all individuals. By contrast, there is genetic diversity of human T cell responses: what may be a target of protective responses to one person may not be for another.

In attempts to solve this challenge, industry has developed complex algorithms to make antigen target predictions based on upstream information. The targets resulting from these predictive methods may prove to have no clinical relevance, may only be relevant to limited patient populations, and may only apply to certain types of T cells.

We have developed a technology, in ATLAS™, that we believe finds the right T cell antigens and addresses the complex challenges that have confounded others in the past.

The ATLAS™ Solution

ATLAS is a first of its kind, proprietary, high throughput screening system that identifies T cell antigens based on natural human immune response from large, diverse populations, providing functional evidence of T cell reactivity and specificity.

ATLAS Flowchart

At the core of ATLAS is the ability to identify what the T cells of people who naturally protect themselves against a disease or pathogen do differently than the T cells of those who don’t. ATLAS winnows what can be as many as several thousand candidate antigens down to a small number of antigens that correlate with natural immunity. A subset of antigens from that group is then selected, with the goal of identifying a small number of antigens for formulation and development into a vaccine candidate that may be protective across diverse ethnic populations.

Since antigens are identified by ATLAS using actual human immune responses to all potential targets, by the time these candidates reach clinical trials, there may be a greater likelihood of success in clinical development.

Since its inception in 2007, Genocea has taken multiple programs from project initiation to animal proof of concept, and two vaccines into the clinic. This represents a dramatically accelerated pace compared with traditional discovery approaches.