PREVENT CANCER PRECLINICAL DRUG DEVELOPMENT PROGRAM - A NOVEL MULTI-ANTIGEN VACCINE (TNBCVAX) TO PREVENT TRIPLE NEGATIVE BREAST CANCER

在这项提案中，申请人建议使用一种同时针对多种肿瘤抗原(TOP2A、IGFIR和HIF-1α)的多抗原预防性疫苗(TNBCvax)，以有效克服抗原阴性的变异逃逸。TOP2A、胰岛素样生长因子-IR和缺氧诱导因子-1α在三阴性乳腺癌中单独过度表达。在初级预防环境中，每种单抗原疫苗在TNBC小鼠模型中都显示出显著的效果。申请者假设，他们的新型主要组织相容性复合体(MHC)II限制性TNBCvax多抗原疫苗在预防携带早期病变的小鼠的TNBC方面将比单个抗原疫苗更有效，并且TNBCvax将诱导强大的T细胞记忆反应，以防止继发性肿瘤细胞的挑战。长期目标是产生强大的临床前数据，以支持TNBCvax的临床使用。最相关的试验设计将是防止TNBC癌前病变患者的肿瘤进展，或防止没有复发证据的原发恶性病变患者的转移。

In this proposal, the applicants propose to use a multiantigen preventive vaccine (TNBCvax) that simultaneously targets multiple tumor antigens (TOP2A, IGF-IR, and HIF-1α) in order to effectively overcome antigen-negative variant escape. Individually, TOP2A, IGF-IR, and HIF-1α are overexpressed in triple-negative breast cancer (TNBC). Each single-antigen vaccine has shown significant efficacy in a mouse model of TNBC in a primary prevention setting. The applicants hypothesize that their novel major histocompatibility complex (MHC) II-restricted TNBCvax multiantigen vaccine will be more effective than individual-antigen vaccines in preventing TNBC in mice carrying existing early lesions, and that TNBCvax will induce a potent T-cell memory response to prevent secondary tumor cell challenges. The long-term goal is to generate strong preclinical data to support the clinical use of TNBCvax. The most relevant trial design will be to prevent tumor progression in patients with TNBC premalignant lesions or to prevent metastasis in subjects with primary malignant lesions where there is no evidence of recurrence.