Biomaterial based breast cancer vaccine

基于生物材料的乳腺癌疫苗

• 批准号: 8830976
• 负责人: David J Mooney
• 金额: $ 36.99万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8830976
• 关键词: Address; Antigens; Autoimmune Diseases; Back; Bacterial Infections; Biocompatible Materials; Biological Models; Biomedical Engineering; Bypass; Cancer Vaccines; Cardiovascular Diseases; Catheters; Cause of Death; Cell Transplants; Cells; Cellular biology; Communicable Diseases; Cues; Cytotoxic T-Lymphocytes; Dendritic Cells; Dendritic cell activation; Development; Devices; Distant; Dose; Economics; Encapsulated; Engineering; Future; Gel; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Home environment; Homing; Housing; Immune; Immune System Diseases; Immune response; Immune system; Immunology; In Situ; Infiltration; Injectable; Injection of therapeutic agent; Lead; Ligands; Lipid A; Malignant Neoplasms; Memory; Modification; Mus; Musculoskeletal Diseases; Needles; Neoplasm Metastasis; Oligonucleotides; Patients; Poly I-C; Polymers; Population; Primary Neoplasm; Property; Recruitment Activity; Recurrence; Research; Rodent Model; Science; Shapes; Site; Structure; System; T-Lymphocyte; Temperature; Testing; Therapeutic; Time; Toll-like receptors; Tooth Diseases; Transplantation; Trauma; Tumor Antigens; Vaccination; Vaccine Design; Vaccines; Woman; Work; base; breast cancer vaccine; cancer type; cryogel; improved; in vivo; lymph nodes; malignant breast neoplasm; men; minimally invasive; novel strategies; prevent; programs; prophylactic; release factor; response; spatiotemporal; standard care; success; trafficking; tumor; vaccine development; vaccine efficacy

DESCRIPTION (provided by applicant): The broad premise underlying our research is that the application of biomaterials science to immunology may dramatically impact how diseases of the immune system are treated in the future. Currently, many experimental cancer vaccines isolate and program immune cells outside the body, and introduce the programmed cells back into the patient (e.g., adoptive T cell transfer, dendritic cell-based vaccinations) to elicit anti-tumor responses. This application proposes a new approach to breast cancer vaccines, in which biomaterials that can be introduced into the body in a minimally invasive manner are used to program, in situ, host dendritic cells to generate a potent immune response. The specific hypothesis to be addressed in this project is that an injectable biomaterial system that mimics bacterial infection, while presenting tumor antigens, can effectively recruit, mature and disperse host dendritic cells capable of stimulating specific T-cell populations and eliciting a strong anti tumor response in the context of breast cancer. This hypothesis will be tested with the following aims: (1) Cryogelation will be utilized to fabricate macroporous gel materials that can be introduced into the body in a minimally invasive manner, while subsequently allowing significant host cell infiltration, (2) DC recruitment factors and Toll Like Receptor ligands will be encapsulated and released in a sustained manner from the gels, and their effects on the types and numbers of DC recruited to the vaccine site will be investigated, and (3) The ability of these cryogels to provide effective prophylactic and therapeutic breast cancer vaccines in rodent models will be tested. The goal of this work is to develop a functional cancer vaccine that can be used to treat women suffering from breast cancer. A successful cancer vaccine would not only be capable of causing regression of a primary tumor, but could also target metastasis in sites distant to the original tumor site. Further, the memory component of the adaptive immune system may provide protection against recurrence in the future. Success in this effort would have a dramatic impact on women suffering from breast cancer, and could potentially have significant impact in the development of vaccines for other types of cancer.

描述（由申请人提供）：我们研究的广泛前提是，生物材料科学在免疫学中的应用可能会极大地影响未来免疫系统疾病的治疗方式。目前，许多实验性癌症疫苗在体外分离和编程免疫细胞，并将编程的细胞引入患者体内（例如，过继性T细胞转移、基于树突细胞的疫苗接种）以引发抗肿瘤应答。该申请提出了一种乳腺癌疫苗的新方法，其中可以以微创方式引入体内的生物材料用于原位编程宿主树突状细胞以产生有效的免疫应答。在该项目中要解决的具体假设是，模拟细菌感染的可注射生物材料系统在呈递肿瘤抗原的同时，可以有效地募集、成熟和分散能够刺激特定T细胞群并引发强抗肿瘤抗体的宿主树突状细胞。 在乳腺癌的背景下的肿瘤反应。将按照以下目的检验这一假设：（1）冷冻干燥将用于制造大孔凝胶材料，其可以以微创方式引入体内，同时随后允许显著的宿主细胞浸润，（2）DC募集因子和Toll样受体配体将被封装并以持续的方式从凝胶中释放，并将研究它们对募集到疫苗位点的DC的类型和数量的影响，以及（3）将测试这些冷冻凝胶在啮齿动物模型中提供有效的预防性和治疗性乳腺癌疫苗的能力。这项工作的目标是开发一种功能性癌症疫苗，可用于治疗患有乳腺癌的妇女。成功的癌症疫苗不仅能够使原发性肿瘤消退，而且还可以靶向远离原始肿瘤部位的转移部位。此外，适应性免疫系统的记忆成分可以提供防止未来复发的保护。这项工作的成功将对患有乳腺癌的妇女产生巨大影响，并可能对其他类型癌症的疫苗开发产生重大影响。