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

在本提案中，申请人建议使用多抗原预防疫苗（TNBCvax），同时针对多种肿瘤抗原（TOP2A， IGF-IR和HIF-1α），以有效克服抗原阴性变异逃逸。单独来看，TOP2A、IGF-IR和HIF-1α在三阴性乳腺癌（TNBC）中过表达。每一种单抗原疫苗在一级预防环境下的TNBC小鼠模型中都显示出显著的疗效。申请人假设他们的新型主要组织相容性复合体（MHC） ii限制TNBCvax多抗原疫苗将比个体抗原疫苗更有效地预防携带现有早期病变的小鼠TNBC，并且TNBCvax将诱导有效的t细胞记忆反应以防止继发性肿瘤细胞攻击。长期目标是产生强有力的临床前数据，以支持TNBCvax的临床使用。最相关的试验设计将是预防TNBC癌前病变患者的肿瘤进展，或预防无复发证据的原发性恶性病变患者的肿瘤转移。

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.