On August 11, 2022 Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vectored immunotherapies, reported the publication in Science Translational Medicine of preclinical and clinical research describing a novel mechanism of action driven by its viral vector-based vaccine platform encoding tumor neoantigens (Press release, NousCom, AUG 11, 2022, View Source [SID1234618183]).
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The publication, entitled ‘Adenoviral based-vaccine promotes neoantigen specific CD8+ T cell stemness and tumor rejection’ demonstrates how Nouscom’s platform when given in combination with anti-PD-1 immunotherapy promotes the expansion and diversification of CD8+ T cells that are specific for the neoantigens encoded by its vaccine. These T cells were shown to exhibit a stem-like phenotype capable of infiltrating the tumor microenvironment and evolving into effector-memory CD8+ T cells.
This mechanism was characterized in a preclinical model of colorectal cancer and confirmed in a Phase 1b trial in metastatic gastrointestinal patients with microsatellite instability-high (MSI-H) tumors who saw durable clinical responses when treated with NOUS-209 in combination with anti-PD1.
Encouraging safety, immunogenicity, clinical efficacy and translational data from a fully enrolled Phase 1b trial were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) and American Society Clinical Oncology (ASCO) (Free ASCO Whitepaper) congresses earlier this year.
Dr. Elisa Scarselli, Chief Scientific Officer of Nouscom, said: "This study published in Science Translational Medicine provides new insights into how our adenoviral vector-based cancer vaccine platform can drive clinical efficacy beyond that seen with checkpoint inhibition alone. Our platform allows us to encode for an unprecedented number of neoantigens and is capable of eliciting both a high quality and quantity T cell response for effective anti-tumor control. This mechanism has been validated in both preclinical studies and observed in patients and furthers our understanding of the clinical potential of adenoviral based cancer vaccines. We remain excited for the start of multiple Phase 2 clinical trials of NOUS-209 in the second half of 2022."
Dr Luigia Pace, Head of the Armenise-Harvard Laboratory of Immunoregulation at the Italian Institute for Genomic Research (IIGM), c/o Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy said: "Adenovirus vectored vaccines, expressing tumor-associated neoantigens is one of the most promising approaches to boost CD8+ T cell dependent anti-tumor immunity. In collaboration with Nouscom, we have uncovered the mechanistic details on how such vaccines may work by expansion and diversification of neoantigen-specific CD8+ T cells with a stem-like phenotype, leading to improved therapeutic responses".
References
A.M. D’Alise et al. Adenoviral Based-Vaccine Promotes Neoantigen Specific CD8+ T Cell Stemness And Tumor Rejection, Science Translational Medicine.
Online publication: www.science.org/doi/10.1126/scitranslmed.abo7604