Abstract
Abstract With its ability to potentially code for any given protein, peptide and fragments, synthetic mRNA has landed itself a broad range of cancer immunotherapy applications, including costimulatory receptors, therapeutic antibodies, vaccines, and cytokines able to change the tumor microenvironment.We have been able to leverage our mRNA platform to generate a vaccine for HPV-associated cervical cancer (CC), as well as an immune-stimulatory cytokine for triple negative breast cancer (TNBC), both diseases that disproportionately affects minorities who do not participate in routine medical screenings and contribute to disparity in mortality beyond individual risk factors.IL-12 is a potent pro-inflammatory type 1 cytokine with potential to enter the clinical practice as immunotherapy for cancer. Its use in the form of recombinant protein and/or DNA plasmid has been hampered by issues with systemic toxicity or protein bioavailability within the tumor. To overcome these roadblocks, we developed a novel secreted single chain IL-12p70 mRNA. Intra-tumoral dosing of this mRNA induced tumor regression in a syngeneic and orthotopic mouse model of TNBC. Almost all cervical cancers are HPV (human papilloma virus) associated. We have developed a therapeutic vaccine, based on a single mRNA coding for two de-risked antigens, that is able to induce a T cell response against the oncogenic proteins E6 and E7 of the most common serotype (HPV16). When injected intramuscularly in mice bearing C3.43 masses, this vaccine suppressed tumor growth and generated immunological memory.Currently, these women’s cancers do not have a cure or an effective standard of care. With an efficacy that relies on a few injections and non-invasive routes of administration, we believe our innovative RNA-based pharmaceuticals might close some treatment gaps. Citation Format: Dan Tse. mRNA-based immunotherapies to treat women's cancers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4154.
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