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.
|Cheung, Alexander S; Zhang, David K Y; Koshy, Sandeep T et al. (2018) Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells. Nat Biotechnol 36:160-169|
|Li, Aileen Weiwei; Sobral, Miguel C; Badrinath, Soumya et al. (2018) A facile approach to enhance antigen response for personalized cancer vaccination. Nat Mater 17:528-534|
|Dellacherie, Maxence O; Li, Aileen W; Lu, Beverly Y et al. (2018) Covalent Conjugation of Peptide Antigen to Mesoporous Silica Rods to Enhance Cellular Responses. Bioconjug Chem 29:733-741|
|Koshy, Sandeep T; Zhang, David K Y; Grolman, Joshua M et al. (2018) Injectable nanocomposite cryogels for versatile protein drug delivery. Acta Biomater 65:36-43|
|Koshy, Sandeep T; Cheung, Alexander S; Gu, Luo et al. (2017) Liposomal Delivery Enhances Immune Activation by STING Agonists for Cancer Immunotherapy. Adv Biosyst 1:|
|Gu, Luo; Mooney, David J (2016) Biomaterials and emerging anticancer therapeutics: engineering the microenvironment. Nat Rev Cancer 16:56-66|
|Li, Weiwei Aileen; Lu, Beverly Ying; Gu, Luo et al. (2016) The effect of surface modification of mesoporous silica micro-rod scaffold on immune cell activation and infiltration. Biomaterials 83:249-56|
|Cheung, Alexander S; Koshy, Sandeep T; Stafford, Alexander G et al. (2016) Adjuvant-Loaded Subcellular Vesicles Derived From Disrupted Cancer Cells for Cancer Vaccination. Small 12:2321-33|
|Koshy, Sandeep T; Desai, Rajiv M; Joly, Pascal et al. (2016) Click-Crosslinked Injectable Gelatin Hydrogels. Adv Healthc Mater 5:541-7|
|Ali, Omar A; Lewin, Sarah A; Dranoff, Glenn et al. (2016) Vaccines Combined with Immune Checkpoint Antibodies Promote Cytotoxic T-cell Activity and Tumor Eradication. Cancer Immunol Res 4:95-100|
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