Genocea to Present Data that Reveal New Understanding of ATLASTM-Identified InhibigenTM Biology at AACR Virtual Annual Meeting II
Inhibigens (inhibitory antigens) are detrimental an otherwise protective immunotherapy
Inhibigens alter the tumor microenvironment and drive tumor hyperprogression
Inhibigens abolish both global and tumor antigen-specific T cell activity
CAMBRIDGE, Mass., June 22, 2020 (GLOBE NEWSWIRE) -- Genocea Biosciences, Inc. (NASDAQ: GNCA), a biopharmaceutical company developing next-generation neoantigen immunotherapies, today presented preclinical data that offers new and important insights into the biology and behavior of inhibitory neoantigens (Inhibigens™) at the American Association for Cancer Research (AACR) Virtual Annual Meeting II from June 22-24. The findings build on previous research presented at SITC 2019 which demonstrated that the presence of an Inhibigen in an otherwise protective immunotherapy can completely reverse anti-tumor responses.
In the preclinical study, pro-tumor Inhibigen effects were found to be correlated with an increasingly immune-suppressive tumor microenvironment (TME), including reduced TILs and enhanced expression of T cell exhaustion markers. Vaccination of tumor-bearing mice with a formulation containing an inhibigen impaired both tumor antigen specific and nonspecific T cell function by blocking their ability to secrete cytokines and kill tumor cells – an effect that abolished T cell responses to beneficial anti-tumor antigens.
“This observed downregulation of anti-tumor cytokine responses could be detrimental to cancer immunotherapies,” said Victoria DeVault, a Genocea research scientist and lead presenter of the results to be shared at AACR. “Thanks to insights gleaned from our uniqu ATLAS platform, we are beginning to understand why immunization with Inhibigens leads to a defective immune response and why proper T cell engagement against the right targets is critical to producing an effective vaccination.”
In addition, the poster presentation revealed that immunization with Inhibigens led to a reduction in T cell receptor (TCR) expression of tumor-specific T cells, which further hindered T cell function and activity needed to produce a robust immune response. The analysis also demonstrated that the Inhibigen-specific responses are not mediated by regulatory T cells – a subset of T cells known to suppress immune responses.
“Taken together, the results add to the growing body of evidence that Inhibigens must be identified and excluded from the rational design of cancer immunotherapies,” said Jessica Baker Flechtner, Chief Scientific Officer of Genocea. “ATLAS allows us to pinpoint the underlying potential reasons why such treatments fail in patients. Armed with this critical knowledge, we can design better and smarter personalized vaccines and cell therapies for more favorable patient outcomes.”
AACR POSTER SESSION TITLE: Immune Response to Therapies 2
Title: Inclusion of inhibitory neoantigens can abolish efficacy of otherwise protective therapeutic anti-tumor vaccines.
Presenter: Victoria DeVault, Ph.D., Genocea Biosciences, Cambridge, MA
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