Developing Biomaterial-based Vaccines for Cancer Immunotherapy

Sidi A. Bencherif

ChE Assistant Professor Sidi A. Bencherif received a $2M R01 grant from the National Institutes of Health for “Overcoming vaccine-associated hypoxia with advanced biomaterials to enhance cancer immunotherapy.“

The project is focused on the development of biomaterial-based vaccines against prostate cancer. Bencherif’s team will integrate advanced injectable hydrogels, hypoxia-fighting nanoparticles, tumor-specific antigens, and immunostimulatory factors. The proposed biomaterials can overcome hypoxia-driven immunosuppression in cancer vaccines and improve therapeutic efficacy.

Overcoming the poor efficacy of tumor cell vaccines will require enhancing activation of the immune system and preventing an immunosuppressive tumor microenvironment such as local hypoxia. In this project, Bencherif will address this critical need by engineering tumor cell vaccines with advanced oxygen-releasing biomaterials (O2-cryogels) to combat hypoxia-driven immunosuppression and improve antitumor immune responses in relevant mouse models of prostate cancer. His preliminary data in mice indicated that: (i) O2-cryogels can reverse local hypoxia and restore the function of key immune cells (dendritic cells; DCs); (ii) once injected into the body, cryogel vaccines efficiently localize transplanted tumor cells, controllably release immunomodulatory factors, and recruit large numbers of DCs from the host; and (iii) elicit a specific and robust vaccine-induced T cell-mediated antitumor immunity. Bencherif and his group will optimize the characteristics of O2-cryogels for maximum antitumor efficacy and safety; and assess their ability to suppress the local hypoxic stress and improve DC recruitment, activation, and homing to the draining lymph nodes. Finally, O2-cryogel vaccines will be tested in prophylactic and therapeutic mouse models of prostate cancer to determine their ability to induce specific, effective, and long-lasting antitumor immune responses. This project may have a sustained impact on the field by defining a new avenue of cancer immunotherapy that operates independently but synergizes with other therapies for the treatment of human cancer.

Bencherif shares, “In collaboration with Professor Michail Sitkovsky, we have planned to develop the next generation of cancer vaccines by combining attenuated tumor cells, advanced macroporous biomaterials, and oxygen as a powerful co-adjuvant. Our proposed biomaterial-based vaccines can boost immune cells and trigger robust and long-lasting antitumor responses.”

The NIH fund will support Bencherif and his collaborators to further optimize and test these novel cancer vaccines in animal models, a critical step for translational research and moving on to the first stage of clinical testing in humans.

Related Departments:Chemical Engineering