From The Editor | April 1, 2021

Inside Repertoire Immune Medicines' T Cell Recognition Of SARS-CoV-2


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

SARs Covid globe iStock-1219889249.jpg

Repertoire Immune Medicines, a clinical-stage biotech company creating a new category of immune therapies for cancer, autoimmunity, and infectious disease, recently announced pre-published data revealing new insights into T cell recognition of SARS-CoV-2. This research indicates how SARS-CoV-2 variants may avoid immune surveillance and informs the design of new T cell-based vaccines that can provide long term immunity. I caught up with Anthony Coyle, Ph.D., President, Research and Development at Repertoire Immune Medicines to learn more about Repertoire’s DECODE platform and the role it played in the T cell recognition of SARS-CoV-2.

Tell us about Repertoire Immune Medicines.

Coyle: Repertoire Immune Medicines is a clinical-stage biotechnology company working to unlock and direct the power of the human immune system to prevent or treat cancer, as well as autoimmune and infectious disease. We are founded on the belief that the repertoire of TCR-antigen codes that drive health and disease represents one of the greatest opportunities for innovation in medical science. Repertoire scientists created and developed the DECODE suite of technologies, which allow in-depth characterization of TCR-antigen pairs, and the ability to rationally design and develop novel targeted immune medicines.

Explain the company’s DECODE platform and the role it played in the T cell recognition of SARS-CoV-2.

Coyle: Current vaccines are primarily designed to induce antibody responses to the spike protein of SARS-CoV-2. However, it is unknown whether humoral immunity induced by these vaccines will lead to long-term protection or adequate coverage of emerging viral variants. Using our proprietary technology discovers disease-causing antigens as well as the T cells that recognize those antigens, Repertoire scientists identified specific viral epitopes from SARS-CoV-2 that were recognized by both CD4+ and CD8+ T cells and described how individuals present these epitopes based on their genetic backgrounds and the expression of their unique human leukocyte antigens (HLA) haplotypes.

The research relates to COVID-19. Explain how this technology platform to make discoveries in cancer, autoimmunity, and other infectious diseases.

Coyle: SARS-CoV-2 isn’t the first disease where we used the DECODE platform. In fact, we are in clinical-stage research in cancer, and have done the same kind of work in type 1 diabetes. The value of decoding the immune synapse is that understanding the antigen and T cell or T cell component that matters, allows us to look across patient populations and create new immune medicines across disease categories. 

Our SARS-CoV-2 research provides insights into how the immune system responds to this infection and suggests mechanisms by which emerging virus variants could escape T cell recognition. Understanding T cell engagement at the precise epitope level should guide the development of novel therapeutic approaches beyond applications to SARS-CoV-2. Further, DECODE is a powerful platform that allows a unique and in-depth understanding of cellular immune responses, and that knowledge is critical for developing the next generation of cellular-based vaccines in society’s long-term fight against the global public health threat of SARS-CoV-2.

We have developed a comprehensive set of experimental tools that allows us to fully decode the immune synapse. We can do this with unique precision, understanding which epitopes are presented by MHC molecules with all their allelic variation. In addition, we can determine which are the immune dominant epitopes that are recognized by T cells or if you will, “what do the T cells see”. Finally, we have developed the state-of-the-art, DNA barcoded tetramer libraries. With this technology, we can identify rare cells in the blood or in tissues and perform single cell analysis to determine the exact phenotype of those cells, their T cell receptor and of course the epitopes that are presented to the T cell. It is only when you understand all these features all of the immune synapse can you then design the next generation of medicines to modify the cellular immunity. This will allow us to identify which cells are the pathogenic cells that cause autoimmunity. In addition, we can now determine how to make T cells that more effectively kill tumors. Finally, these technologies provide insights into understanding the immune response to pathogens and infectious agents

What is next for Repertoire Immune Medicines?

Coyle: Repertoire Immune Medicines is leading what we believe will be a revolution in medicine based on cellular immunity.  We are experts at not only discovering and characterizing antigen-TCR pairs with great specificity, which is the basis for decoding the immune synapse. Our scientists also have developed novel technologies that enable us to rationally design and clinically develop an entirely new class of targeted immune medicines.

Today we have two antigen repertoires, one directed at multiple solid tumors including melanomas, and another directed at head and neck cancer, and HPV-16 antigens. We are applying our science to PRIME IL-12 and PRIME IL-15, with one IND for each. We also can combine IL-15 and IL-12, which is the first time anyone has been able to put two cytokines together.