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 insi
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 unique 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
Abstract 7039 / Poster 6680
Title: Inclusion of inhibitory neoantigens can abolish efficacy of otherwise protective therapeutic anti-tumor vaccines.
Presenter: Victoria DeVault, Ph.D., Genocea Biosciences, Cambridge, MA
Date: June 22, 2020
Time: 9:00 a.m. – 6:00 p.m. EDT
About Genocea Biosciences, Inc.
Genocea’s mission is to conquer cancer by developing personalized cancer immunotherapies in multiple tumor types. Our unique ATLAS™ platform comprehensively profiles each patient’s T cell responses to potential targets, or antigens, on the tumor. ATLAS enables us to optimize the neoantigens for inclusion in our immunotherapies and exclude inhibitory antigens that can exert an immunosuppressive effect. We are advancing two ATLAS-enabled programs: GEN-009, our neoantigen vaccine for which we are conducting a Phase 1/2a clinical trial and expect preliminary clinical results in the third quarter of 2020, and GEN-011, our neoantigen-specific cell therapy using T cells derived from peripheral blood for which we expect to conduct a Phase 1/2a clinical trial with preliminary clinical results in mid-2021. To learn more, please visit www.genocea.com.
Forward-Looking Statements
This press release includes forward-looking statements, including statements relating to GEN-009 and GEN-011, within the meaning of the Private Securities Litigation Reform Act. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Genocea cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties that change over time. Applicable risks and uncertainties include those identified under the heading “Risk Factors” included in Genocea’s Annual Report on Form 10-K for the year ended December 31, 2019 and any subsequent SEC filings. These forward-looking statements speak only as of the date of this press release and Genocea assumes no duty to update forward-looking statements, except as may be required by law.
Investor Contact:
Dan Ferry
617-430-7576
daniel@lifesciadvisors.com
