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.
One half of all men, and one third of all women in the US will have cancer in their lifetime, and cancer remains a major cause of death. The goal of these studies is to take a bioengineering approach to design vaccines to both prevent and treat cancer. The biomaterials developed in this project may provide more practical and effective vaccines than the cell-based vaccines currently under development.
|Brudno, Yevgeny; Silva, Eduardo A; Kearney, Cathal J et al. (2014) Refilling drug delivery depots through the blood. Proc Natl Acad Sci U S A 111:12722-7|
|Ali, Omar A; Verbeke, Catia; Johnson, Chris et al. (2014) Identification of immune factors regulating antitumor immunity using polymeric vaccines with multiple adjuvants. Cancer Res 74:1670-81|
|Kim, Jaeyun; Li, Weiwei Aileen; Sands, Warren et al. (2014) Effect of pore structure of macroporous poly(lactide-co-glycolide) scaffolds on the in vivo enrichment of dendritic cells. ACS Appl Mater Interfaces 6:8505-12|
|Kim, Jaeyun; Bencherif, Sidi A; Li, Weiwei Aileen et al. (2014) Cell-friendly inverse opal-like hydrogels for a spatially separated co-culture system. Macromol Rapid Commun 35:1578-86|
|Koshy, Sandeep T; Ferrante, Thomas C; Lewin, Sarah A et al. (2014) Injectable, porous, and cell-responsive gelatin cryogels. Biomaterials 35:2477-87|
|Chaudhuri, Ovijit; Koshy, Sandeep T; Branco da Cunha, Cristiana et al. (2014) Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nat Mater 13:970-8|
|Gu, Luo; Hall, David J; Qin, Zhengtao et al. (2013) In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles. Nat Commun 4:2326|