Abstract B24: Development of targeted T-cell cancer immunotherapies based on a novel enantiomeric cationic lipid that promotes antigen cross-presentation and upregulation of type I interferons


 The enantiomeric cationic lipid R-DOTAP nanoparticle platform (Versamune®) was reported (Gandhapudi et. al. 2019, J. Immunol.) to promote cross presentation of multi-epitope human papilloma virus (HPV) antigens and upregulation of Type I interferons, leading to induction of high levels of antigen-specific cytolytic polyfuctional CD8+ T-cells in vivo and complete regression of TC-1 tumors in preclinical models. In two ongoing Phase 2 human clinical trials (ASCO 2022), the early data in a group of the first 60 patients receiving PDS0101 (Versamune® plus HPV16 peptide mix) and who had previously failed standard of care suggests translation of the established mechanism of action into humans resulting in the induction of tumor-specific, clinically effective immune responses. In refractory and difficult-to-treat HPV-related cancers, improved patient survival and tumor shrinkage has been demonstrated. In this study we demonstrate expansion of the Versamune® platform to the treatment of non-viral associated cancers. We have developed Versamune® based drug formulations containing novel multi-epitope peptide sequences of the TARP (T-Cell receptor gamma chain Alternate Reading frame Protein) antigen expressed in 100% of adult and pediatric AML (acute myelogenous leukemia), over 90% of prostate cancers and over 50% of breast cancers. We have also developed Versamune® based drug formulations containing modified sequences of novel Mucin 1 oncoprotein (MUC1) agonist peptide antigens that are over expressed in multiple solid tumors. Using humanized HLA-A2 transgenic mice, we show that the Versamune® platform similarly promotes cross presentation of the non-viral antigens resulting in equally high levels of antigen-specific CD8+ T-cells as observed with HPV. These data demonstrate superior immunogenicity in breadth and potency of vaccine-induced immune responses, supporting progression of the targeted T-cell immunotherapies into human clinical trials.
 Citation Format: Siva K Gandhapudi, Karuna Sundarapandiyan, Martin Ward, Afsheen Fatima, Mania Dorrani, Mary Banoub, Joe Dervan, Lauren Wood, Greg Conn, Jerold G Woodward. Development of targeted T-cell cancer immunotherapies based on a novel enantiomeric cationic lipid that promotes antigen cross-presentation and upregulation of type I interferons [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B24.