Therapeutic supramolecular tubustecan hydrogel combined with checkpoint inhibitor elicits immunity to combat cancer
The clinical benefit of PD-1/PD-L1 blockade immunotherapy is substantially restricted by insufficient infiltration of T lymphocytes into tumors and compromised therapeutic effects due to immune-related adverse events following systemic administration. Some chemotherapeutic agents have been reported...
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Veröffentlicht in: | Biomaterials 2021-12, Vol.279, p.121182-121182, Article 121182 |
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Sprache: | eng |
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Zusammenfassung: | The clinical benefit of PD-1/PD-L1 blockade immunotherapy is substantially restricted by insufficient infiltration of T lymphocytes into tumors and compromised therapeutic effects due to immune-related adverse events following systemic administration. Some chemotherapeutic agents have been reported to trigger tumor-associated T cell responses, providing a promising strategy to achieve potent immune activation in a synergistic manner with PD-1 blockade immunotherapy. In light of this, a localized chemoimmunotherapy system was developed using an anti-cancer drug-based supramolecular polymer (SP) hydrogel to “re-edit” the host's immune system to combat cancer. This in situ forming injectable aPD1/TT6 SP hydrogel serves as a drug-delivery depot for sustained release of bioactive camptothecin (CPT) and aPD1 into the tumor microenvironment, priming the tumor for robust infiltration of tumor-associated T cells and subsequently prompting a response to the immune checkpoint blockade. Our in vivo results demonstrate that this chemoimmunotherapy hydrogel provokes a long-term and systemic anticancer T cell immune response, which elicits tumor regression while also inhibiting tumor recurrence and potential metastasis.
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ISSN: | 0142-9612 1878-5905 |
DOI: | 10.1016/j.biomaterials.2021.121182 |