Biomaterial based breast cancer vaccine

描述(申请人提供)：我们研究的基本前提是，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T细胞转移、树突状细胞疫苗接种)以诱导抗肿瘤反应。这项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被用来原位编程宿主树突状细胞，以产生强大的免疫反应。这个项目要解决的具体假设是，一个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，可以有效地招募、成熟和分散宿主树突状细胞，能够刺激特定的T细胞群并激发出强大的抗肿瘤抗体。 乳腺癌背景下的肿瘤反应。将检验这一假设，目的如下：(1)冷冻作用将被用来制造能够以微创方式引入体内的大孔凝胶材料，同时允许显著的宿主细胞渗透，(2)DC募集因子和Toll样受体配体将以持续的方式被包裹并从凝胶中释放，并且它们对募集到疫苗部位的DC的类型和数量的影响将被研究，(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女性。一种成功的癌症疫苗不仅能够导致原发肿瘤的消退，还可以靶向远离原始肿瘤部位的转移。此外，适应性免疫系统的记忆组件可能会提供保护，防止未来复发。这一努力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疫苗的开发产生重大影响。

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.