Genocea to Present Novel Preclinical Inhibigen™ Data at AACR Annual Meeting 2021
April 10, 2021 at 08:30 AM EDT
Pro-tumor effects detected as early as four days after Inhibigen administration
Insights into Inhibigen biology may yield new therapeutic targets to address immunotherapy resistance
CAMBRIDGE, Mass., April 10, 2021 (GLOBE NEWSWIRE) -- Genocea Biosciences, Inc. (NASDAQ: GNCA), a biopharmaceutical company developing next-generation neoantigen immunotherapies, today presented preclinical data that offers new insights into Inhibigen™-associated responses and continues to underscore the detrimental impact of their inclusion in cancer immunotherapies at the American Association for Cancer Research (AACR) Annual Meeting 2021 from April 10-15. The findings – powered by Genocea’s proprietary ATLAS™ platform – further validate previous research presented at SITC 2020 and published in Cancer Discovery, together revealing that the presence of an Inhibigen (antigen uniquely identifiable by ATLAS as dampening anti-tumor immune responses) in an otherwise protective immunotherapy can completely reverse the therapy’s intended anti-tumor responses.
The new data show that therapeutic vaccination of tumor-bearing mice with a single Inhibigen caused their tumors to hyperprogress, in contrast to a vaccine containing stimulatory antigens that protected them against tumor growth. The combination of this single Inhibigen with the otherwise-protective vaccine abrogated vaccine efficacy and returned tumor growth to levels of unvaccinated mice. The Inhibigen-associated effects included dampening of T cell immune responses as early as four days after a single dose, and a reversal of the infiltration of both lymphoid and myeloid populations into the tumor microenvironment. These data suggest that Inhibigen-specific responses not only dampen systemic immunity, but also revert tumor microenvironments to an immune-cold state – a feature of early-stage tumor growth.
“Our data add to a growing body of preclinical and clinical evidence confirming that Inhibigens are not innocent bystanders, but rather they can reverse the beneficial effects of cancer immunotherapies,” said Hanna Starobinets, a scientist at Genocea and lead presenter at the AACR meeting. “While Genocea continues to exclude Inhibigens from its immunotherapy candidates, ongoing studies aim to further allow us to understand and overcome immunotherapy resistance.”
Genocea previously demonstrated that Inhibigen vaccination could stifle immune responses to other antigens co-formulated in a vaccine, and that the effect could not be reversed through combination therapy with immune checkpoint inhibitors (ICI). Moreover, early data from ATLAS profiling of T cell responses in patients with cancer showed that the relative proportion of Inhibigen- and neoantigen-specific responses prior to treatment appeared to predict clinical efficacy of subsequent ICI therapy.
“While we avoid Inhibigens in our current immunotherapy candidates, our preclinical work is focused on understanding the mechanisms of Inhibigen-associated immune suppression so that we may ultimately develop new treatments that can revert the phenotype in the context of immuno-oncology and perhaps even drive the phenotype in other contexts, such as autoimmune diseases,” said Jessica Baker Flechtner, Chief Scientific Officer of Genocea. “This important nuance – the possibility for Inhibigens to be used for therapeutic benefit – is one that we look forward to exploring further as we continue to gain insights into their underlying biology and function.”
AACR POSTER SESSION CATEGORY: Inflammation, Immunity, and Cancer
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