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1100 Immunovirotherapy with the codon-modified influenza virus CodaLytic™ modulates the quality of the tumor immune infiltrate in support of anti-tumor immunity

BackgroundVirotherapeutics leverage oncolytic and pro-inflammatory properties to ultimately engage multiple mechanisms of action that lead to holistic modulation of the tumor microenvironment (TME) and induction of anti-tumor immunity. As such, they serve as off-the-shelf in situ cancer vaccines to...

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Published in:Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 1), p.A1211-A1211
Main Authors: Zhao, Yiwen, Jahan, Nusrat, Blagovic, Katarina, Mueller, Steffen, Robert Coleman, J, Kaufmann, Johanna K
Format: Article
Language:English
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Summary:BackgroundVirotherapeutics leverage oncolytic and pro-inflammatory properties to ultimately engage multiple mechanisms of action that lead to holistic modulation of the tumor microenvironment (TME) and induction of anti-tumor immunity. As such, they serve as off-the-shelf in situ cancer vaccines to generate a personalized immune response. We have previously introduced CodaLytic, a codon-modified influenza virus, as an efficient kick-starter of the cancer immunity cycle in several murine models with different baseline immune contexture and in human tumor explant cultures. Here, we are presenting a deeper dive into the immune cell composition infiltrating syngeneic mouse tumors after treatment with CodaLytic.MethodsEffects on the TME were measured after intratumoral administration of 108 PFU CodaLytic as monotherapy and in combination with immune checkpoint blockade (ICB) and/or chemotherapy in orthotopic EMT6 and 4T1 triple-negative breast cancer, subcutaneous B16-F10 melanoma and MC38 colon cancer mouse models. Tumors were harvested and dissociated for characterization of immune infiltrate by flow cytometry after ≥2 doses of virus and after onset of efficacy based on tumor volume in at least one experimental group.ResultsAcross all models, virus treatment increased tumor infiltration with T and antigen-presenting cells, which could be further boosted by addition of ICB. Both total CD3+ T and importantly CD8+ T cells were recruited to tumors in response to treatment and their frequency within the immune infiltrate correlated directly with tumor volumes (CD3+: MC38 R2=0.58, p
ISSN:2051-1426
DOI:10.1136/jitc-2023-SITC2023.1100