ChE PhD Dissertation Defense: Alexandra Nukovic

Name:
Alexandra Nukovic

Title:
Optimizing the Immunogenicity of an Oxygen-Generating Cryogel Vaccine Platform Against Prostate Cancer

Date:
03/17/2026

Time:
10:00:00 AM

Committee Members:
Prof. Stephen Hatfield (Advisor)
Prof. Sidi Bencherif
Prof. Kara Spiller
Prof. Rebecca Carrier
Prof. Allison Dennis

Location:
Hastings 209

Abstract:
Therapeutic cancer vaccines have been a promising avenue of research to boost patients’ own immune system to fight cancer, targeting tumor eradication and inducing long-term immunological memory. However, promising vaccine candidates have had limited success in clinical trials due to immunosuppressive mechanisms and insufficient delivery methods to overcome tolerance to tumor antigens.  Cryogel delivery scaffolds have already been established as a promising delivery vehicle for cancer vaccines, due to their biocompatibility and macroporous nature, which allow effective delivery to infiltrating cells; however, cryogel-based vaccines are limited by rapid, diffusion-mediated burst release of encapsulated recombinant proteins and local immunosuppressive hypoxia within the scaffold. Herein, biochemical strategies are explored to improve hyaluronic acid-glycidyl methacrylate (HAGM) cryogels as effective delivery vehicles for a therapeutic prostate cancer vaccine.

First, the degradation of cryogels via polymer oxidation was investigated as a potential strategy to control in vivo degradation and cargo delivery. Degradation of HAGM is hindered by the slow hydrolysis of the polymer after free-radical polymerization, yielding dense polymer networks that endow cryogels with mechanical robustness. Ideally, the degradation and resorption of HAGM cryogels should align with the timing of their application. Oxidation of the polymer facilitates degradation through alkaline hydrolysis. This work emphasizes the complexities involved in modeling degradation kinetics, demonstrates that polymer degradation enhances the in vivo delivery of the model antigen ovalbumin, and highlights the potential of cryogels as biocompatible, degradable, and injectable scaffolds for biomedical uses, reducing long-term side effects and removing the need for surgical removal.

Next, a cryogel-based vaccine platform was explored to improve immunological memory to an anti-cancer vaccine for prostate cancer. Click conjugation of a tumor-associated protein within the cryogel improved antigen delivery, supporting strong cellular memory responses. Meanwhile, the inclusion of oxygen generation within the cryogel serves as a powerful co-adjuvant to boost humoral immunity. Cryogel-based vaccination elicited a robust anti-cancer response, inhibiting tumor growth. Together, these biochemical strategies prove to be key improvements that could help tailor cryogel-based delivery of immunological agents to improve patient responses

Alexandra (Alex) Nukovic is currently a PhD candidate in her 5th year of study in the Department of Chemical Engineering at Northeastern University. She has previously graduated with a Bachelor of Science degree in Bioengineering from Clemson University. Alex has been a member of the Biomedical Engineering Society, the Society of Biomaterials, and the American Association for Cancer Research. She is currently a member of the Association for Women in Science.