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Oxygen-generating cryogel vaccines help overcome tumor antigen tolerance and induce durable antitumor immunity in
Alexandra Nukovic1,2, Khushbu Bhatt3, Thibault Colombani1,4
1Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA.
Abstract:
Therapeutic cancer vaccines represent a promising approach to boost patients' own immune system to fight cancer; however, they have shown limited success in clinical trials largely due to insufficient antigen delivery to overcome tolerance and hypoxia-mediated immunosuppression. Cryogel-based delivery scaffolds offer a promising platform for cancer vaccines due to their biocompatibility and macroporous structure, enabling effective delivery to infiltrating antigen-presenting cells. However, these systems are limited by rapid, diffusion-mediated burst release of encapsulated proteins and local hypoxia-driven immunosuppression. Click conjugation of a tumor-associated protein within cryogel-based vaccines, combined with an O2-generating platform (Click O2-CryogelVAX), overcomes immunosuppression and weak antigenicity, and primes effective antitumor immunity. Sustained antigen delivery promotes cellular memory and Th1-driven responses, while O2 release enhances humoral immunity. Together, Click O2-CryogelVAX supports a robust antitumor response and prolongs survival in a therapeutic prostate cancer model, supporting further investigation as an effective delivery platform for cancer vaccines.
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