Solid tumors are protected from antitumor immune responses due to their hypoxic microenvironments. Weakening hypoxia‐driven immunosuppression by hyperoxic breathing of 60% oxygen has shown to be effective in unleashing antitumor immune cells against solid tumors. However, efficacy of systemic oxygenation is limited against solid tumors outside of lungs and has been associated with unwanted side effects. As a result, it is essential to develop targeted oxygenation alternatives to weaken tumor hypoxia as novel approaches to restore immune responses against cancer. Herein, injectable oxygen‐generating cryogels (O2‐cryogels) to reverse tumor‐induced hypoxia are reported. These macroporous biomaterials are designed to locally deliver oxygen, inhibit the expression of hypoxia‐inducible genes in hypoxic melanoma cells, and reduce the accumulation of immunosuppressive extracellular adenosine. The data show that O2‐cryogels enhance T cell‐mediated secretion of cytotoxic proteins, restoring the killing ability of tumor‐specific cytotoxic T lymphocytes, both in vitro and in vivo. In summary, O2‐cryogels provide a unique and safe platform to supply oxygen as a coadjuvant in hypoxic tumors and have the potential to improve cancer immunotherapies.
Cryogenic processes are increasingly being utilized to create unique polymeric materials that tackle challenges mainly in the biomedical arena, environmental science, and field of food technology [...]
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented global health crisis, resulting in a critical need for effective vaccines that generate protective antibodies. Protein subunit vaccines represent a promising approach but often lack the immunogenicity required for strong immune stimulation. To overcome this challenge, we first demonstrate that advanced biomaterials can be leveraged to boost the effectiveness of SARS‐CoV‐2 protein subunit vaccines. Additionally, we report that oxygen is a powerful immunological co‐adjuvant and has an ability to further potentiate vaccine potency. In preclinical studies, mice immunized with an oxygen‐generating COVID‐19 cryogel‐based vaccine (O
2
‐Cryogel
VAX
) exhibited a robust Th1 and Th2 immune response, leading to a sustained production of highly effective neutralizing antibodies against the virus. Even with a single immunization, O
2
‐Cryogel
VAX
achieved high antibody titers within 21 days, and both binding and neutralizing antibody levels were further increased after a second dose. Engineering a potent vaccine system that generates sufficient neutralizing antibodies after one dose is a preferred strategy amid vaccine shortage. Our data suggest that this platform is a promising technology to reinforce vaccine‐driven immunostimulation and is applicable to current and emerging infectious diseases.
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