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; 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.

在此提案中，申请人建议使用多蛋白预防疫苗（TNBCVAX），该预防疫苗（TNBCVAX）仅针对多种肿瘤抗原（TOP2A，IGF-IR和HIF-1α），以有效克服抗原阴性变体逃生。单独的TOP2A，IGF-IR和HIF-1α在三阴性乳腺癌（TNBC）中过表达。每种单抗原疫苗在主要预防环境中的小鼠TNBC模型中显示出显着的有效性。申请人假设他们的新型主要组织相容性复合物（MHC）II限制的TNBCVAX多敏疫苗疫苗将比单个抗原疫苗在防止现有早期病变的小鼠中更有效，并且TNBCVAX会引起潜在的T-cell记忆力对预防二级细胞的潜在记忆响应。长期目标是生成强大的临床前数据，以支持TNBCVAX的临床使用。最相关的试验设计是防止TNBC前病变患者的肿瘤进展，或者预防没有复发证据的主要恶性病变受试者的转移。