{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:04:48Z","timestamp":1790661888074,"version":"4.1.0"},"reference-count":164,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp;amp; Transla Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The tumor\u2010associated extracellular matrix (ECM) and glycocalyx form a dynamic barrier that provides physical shielding and immunosuppressive signaling, leading to therapeutic resistance. A growing body of evidence supports enzyme\u2010based strategies to remodel these barriers and improve therapeutic access to tumors. This review examines enzymes that act as \u201cpath cleansers\u201d by cleaving components of the ECM or the glycocalyx to restore the efficacy of immunotherapies. Moreover, some enzymes may exert effects beyond barrier remodeling, including modulation of signaling pathways, enhancement of immune responses, or even direct effects on the tumor. In this review, barrier\u2010remodeling enzymes, categorized into different classes, are discussed as potential adjuncts to cancer immunotherapy. This review also highlights the bioengineering approaches and the delivery strategies used to enhance tumor specificity, efficacy, and safety. While such therapeutic strategies show promising outcomes, the evidence hierarchy and potential translational risks are also discussed. Improved patient stratification and computationally guided enzyme discovery and protein engineering, including strategies to reduce immunogenicity, can facilitate the clinical translation of enzyme\u2010assisted immunotherapy.<\/jats:p>","DOI":"10.1002\/btm2.70180","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:44:37Z","timestamp":1790660677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enzyme\u2010mediated remodeling of the extracellular matrix and glycocalyx to enhance immunotherapy in solid tumors"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-1259","authenticated-orcid":false,"given":"Navid","family":"Mirmohammadsadegh","sequence":"first","affiliation":[{"name":"Department of Drug and Food Control, Faculty of Pharmacy Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5666-8339","authenticated-orcid":false,"given":"Mohsen","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Drug and Food Control, Faculty of Pharmacy Tehran University of Medical Sciences  Tehran Iran"},{"name":"Nutraceutics Research Center Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"6850","DOI":"10.1111\/febs.15776","article-title":"A guide to the composition and functions of the extracellular matrix","volume":"288","author":"Karamanos NK","year":"2021","journal-title":"FEBS J"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41568-020-00329-7","article-title":"The matrix in cancer","volume":"21","author":"Cox 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