Claire Rosean, Ph.D., Senior Scientist at Immunomic Therapeutics. In this video, she speaks about the AACR 2022 Abstract – 2052 / 10 – ITI-3000 targeting of the large T antigen of Merkel cell polyomavirus elicits potent CD4+ T cell responses, tumor inhibition, and provides rationale for first-in-human trial.
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Overview:
The majority of Merkel cell carcinomas (MCC), a rare and deadly type of neuroendocrine skin cancer, are caused by Merkel cell polyomavirus (MCPyV). MCPyV integrates into the host genome, causing infected cells to express a shortened form of the viral large T antigen (LT), making LT an appealing target for therapeutic cancer vaccines. We created a cancer vaccine that stimulates powerful, antigen-specific CD4+ T cell responses to MCPV-LT. We used our nucleic acid platform, UNITETM (UNiversal Intracellular Targeted Expression), which combines a tumor-associated antigen with lysosomal-associated membrane protein 1 to activate antigen-specific CD4+ T cells in vivo (LAMP1). This lysosomal targeting method leads to improved antigen presentation and a more balanced T cell response. LTS220A, which encodes a mutant version of MCPV-LT with reduced pro-oncogenic characteristics, was introduced into the UNITETM platform. Vaccination with LTS220A-UNITETM (ITI-3000) produced antigen-specific CD4+ T cells sufficient to prevent tumor growth in pre-clinical tests, and this impact was dependent on their ability to produce IFN. Furthermore, ITI-3000 created a favorable tumor microenvironment (TME), including increased numbers of CD4+ and CD8+ T cells, as well as NK and NKT cells. These findings strongly imply that, in pre-clinical investigations, DNA vaccination using the UNITETM platform boosts CD4+ T cell responses to MCPV-LT, resulting in robust anti-tumor immune responses. We intend to conduct a first-in-human (FIH) open-label Phase 1 research to assess the safety, tolerability, and immunogenicity of ITI-3000 in patients with polyomavirus-positive MCC. The PharmaJet Stratis® needle-free injection system will be used to provide up to four intramuscular vaccines of 4mg of ITI-3000 to patients. The key goals will be safety and tolerability, as well as the observation of dose-limiting toxicities, significant adverse events, conventional clinical assessments, and safety laboratory markers. The vaccine
‘s immunogenicity will be assessed utilizing ELISpot and flow cytometry tests on T cell activation in peripheral blood.