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

预防癌症临床前药物开发计划 - 预防三阴性乳腺癌的新型多抗原疫苗 (TNBCVAX)

• 批准号: 10678625
• 负责人: CHINTHALAPALLY RAO
• 金额: $ 63.1万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-16 至 2024-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10678625
• 关键词: Address; Antigens; Clinical; Data; Development; Goals; Immune response; Immunologic Memory; Individual; Lesion; Major Histocompatibility Complex; Malignant - descriptor; Malignant Neoplasms; Mus; Neoplasm Metastasis; Patients; Preclinical Drug Development; Preventive; Preventive vaccine; Primary Prevention; Program Development; Recurrence; Survival Rate; T memory cell; TOP2A gene; Transgenic Mice; Tumor Antigens; Vaccine Antigen; Vaccines; Variant; efficacy evaluation; malignant breast neoplasm; mouse model; neoplastic cell; novel; overexpression; pre-clinical; premalignant; prevent; protective effect; response; trial design; triple-negative invasive breast carcinoma; tumor progression

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.

在该提案中，申请人提出使用同时靶向多种肿瘤抗原（TOP 2A、IGF-IR和HIF-1α）的多抗原预防性疫苗（TNBCvax），以有效克服抗原阴性变异逃逸。TOP 2A、IGF-IR和HIF-1α在三阴性乳腺癌（TNBC）中单独过表达。每种单抗原疫苗在一级预防环境中的TNBC小鼠模型中显示出显著的功效。申请人假设，他们的新型主要组织相容性复合体（MHC）II限制性TNBC vax多抗原疫苗在预防携带现有早期病变的小鼠中的TNBC方面将比个体抗原疫苗更有效，并且TNBC vax将诱导有效的T细胞记忆应答以预防继发性肿瘤细胞攻击。长期目标是生成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受试者的转移。