TO TITLE: A NOVEL MRNA VACCINE TO PREVENT TRIPLE NEGATIVE BREAST CANCERIDIQ TITLE: PREVENT CANCER PRECLINICAL DRUG DEVELOPMENT PROGRAM: PRECLINICAL EFFICACY AND INTERMEDIATE ENDPOINT BIOMARKERS

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Principal Investigator: Chinthalapally V. Rao
Organization: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
Fiscal Year: 2024
Award: $764,880
Funding agency: National Cancer Institute

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by the absence of estrogen receptors (ER), progesterone receptors (PR), and HER2 receptors. Patients with TNBC have a significantly lower 5-year survival rate compared to other breast cancer types. Molecular studies have identified numerous genes overexpressed in TNBC, which could serve as potential targets for preventive vaccines.
Most existing vaccines target advanced disease stages, where immune suppression hinders efficacy. Preliminary data show that peptide vaccines targeting overexpressed self-antigens in TNBC can elicit strong immune responses. A multivalent vaccine, incorporating epitopes from multiple overexpressed proteins has shown greater efficacy in animal models than single-antigen vaccines.
This project will develop a multi-antigen vaccine targeting TOP2A, cyclin E2, and KIF15, all overexpressed in TNBC. The new vaccine will be tested in vivo in syngeneic transplantable and in orthotopic TNBC mouse models.

Terms: <Animal Model><Animal Models and Related Studies><Antigenic Determinants><Autoantigens><Autologous Antigens><Binding Determinants><Biological Markers><Breast><Breast Cancer><CCNE2><CCNE2 Protein><CCNE2 gene><CGE2><CYCE2><Cancers><Cyclin E2 Gene><Data><Dose><ERBB2><ERBB2 gene><Epitopes><Estrogen Receptors><Evaluation><G1/S-Specific Cyclin E2><Genes><HER -2><HER-2><HER2><HER2 Genes><HER2/neu><Immune response><Immunization><Immunological response><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><In vivo analysis><Individual><Isogeneic Homograft><Isogeneic Transplantation><Isogenic transplantation><Isograft><Malignant Breast Neoplasm><Malignant Neoplasms><Malignant Tumor><Mice><Mice Mammals><Modeling><Molecular><Murine><Mus><NEU Oncogene><NEU protein><Oncogene ErbB2><Patients><Peptide Vaccines><Pre-clinical Drug Testing/Development><Preclinical Drug Development><Preclinical Drug Testing/Development><Preventative vaccine><Prevention><Preventive vaccine><Production><Progesterone Receptors><Progestin Receptors><Program Development><Prophylactic vaccine><Proteins><RNA vaccine><RNA-based vaccine><Receptor Protein><Route><Schedule><Self-Antigens><Survival Rate><Syngeneic Homograft><Syngeneic Transplantation><TKR1><TNBC><TOP2><TOP2A><TOP2A gene><TP2A><Vaccine Antigen><Vaccines><advanced disease><advanced illness><bio-markers><biologic marker><biomarker><c-erbB-2><c-erbB-2 Genes><c-erbB-2 Proto-Oncogenes><cancer type><cyclin E2><design><designing><erbB-2 Genes><herstatin><host response><immune suppression><immune suppressive activity><immune suppressive function><immune system response><immunogenicity><immunoresponse><immunosuppressive activity><immunosuppressive function><immunosuppressive response><in vivo evaluation><in vivo testing><mRNA vaccine><mRNA-based vaccine><malignancy><malignant breast tumor><model of animal><mouse model><murine model><neoplasm/cancer><neu Genes><new vaccines><next generation vaccines><novel><novel vaccines><overexpress><overexpression><pre-clinical drug development><pre-clinical efficacy><preclinical efficacy><prevent><preventing><receptor><triple-negative breast cancer><triple-negative invasive breast carcinoma><tumor>