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bioRxiv · 10.1101/2023.03.23.533909

Cancer Immunotherapy through Tissue Adhering Polymers

Borthwick, N. J.·Maikawa, C. L.·Weller, S.·Andresen, T. L.·Hansen, A. E.·Autzen, A. A. A.
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Abstract

TLR 7/8 agonists are highly potent immunostimulators, though their clinical translation has been met with mixed success, due to their high toxicity as a result of an unregulated systemic immune activation. There is enormous potential to augment cancer immunotherapies with synthetic TLR 7/8 agonists, though a thorough control of pharmacokinetics and localization is needed for the general use of TLR 7/8 agonists in cancer immunotherapy. Herein, we control localization of TLR 7/8 agonists, by exploiting the extensive tissue retention of poly(acrylic acid-co-styrene). In a murine CT26 model, we find that covalently attaching TLR 7/8 agonists to the copolymer allows for retaining the drug in the tumor microenvironment for at least 15 weeks, after intratumoral injection, and results in a curative monotherapy. The copolymer itself is a new avenue for attaining prolonged tissue rentention for covalently attached drugs.

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Borthwick, N. J., Maikawa, C. L., Weller, S., Andresen, T. L., Hansen, A. E., Autzen, A. A. A.. 2023-03-24. Cancer Immunotherapy through Tissue Adhering Polymers. https://doi.org/10.1101/2023.03.23.533909

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