Bioorthogonal chemistry-enabled multiscale engineering of cancer immunotherapy.

Authors

Weiran Song, Meiling Wang, Shutong Lin, Feng Zhou, Zenan Yang, Feilun Deng, Fangmin Chen, Lingfang Hao, Zhiai Xu, Haijun Yu, Yi Lai

Published in

Advanced drug delivery reviews. Pages 115998. Nov 11, 2026. Epub Nov 11, 2026.

Abstract

Immunotherapy has revolutionized clinical cancer management by harnessing endogenous or engineered immune responses to eliminate tumors. However, durable and safe responses in many solid tumors remain limited by the difficulty of directing potent immunomodulation to defined tumor lesions, immune-cell interfaces, and lymphoid tissues while avoiding systemic immune-related toxicity. Bioorthogonal chemistry provides a chemical strategy to address this limitation by installing non-native reactive handles in biological systems, where they undergo selective reactions to generate covalent linkages, localized activation, or functional assembly under physiological conditions. In cancer immunotherapy, these reactions can chemically label cells and biomolecules, bridge tumor-immune interfaces, anchor or assemble therapeutic platforms within tumors, and activate immunomodulators at disease-relevant sites. In this review, we first summarize the bioorthogonal reaction principles underlying chemical tagging, covalent ligation, controlled cleavage/decaging, and in situ assembly. We then discuss how these chemistries support multiscale immune engineering, from immune-tumor interface regulation and tumor microenvironment remodeling to antigen-presenting cell programming and lymph node-targeted immune priming. Finally, we highlight current translational progress, remaining challenges, and future directions for clinical implementation of bioorthogonal strategies in cancer immunotherapy. By connecting reaction design with immune-engineering function, this Review provides a framework for understanding bioorthogonal chemistry as a site-confined and multiscale strategy for cancer immunotherapy.

PMID:
43014549
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.