{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:31Z","timestamp":1792790371001,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,27]]},"group-title":"Bioengineering","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01CA238268"],"award-info":[{"award-number":["R01CA238268"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K99CA303346"],"award-info":[{"award-number":["K99CA303346"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Damon Runyon Cancer Research Foundation","award":["DRG-2529-24"],"award-info":[{"award-number":["DRG-2529-24"]}],"id":[{"id":"https:\/\/ror.org\/01gd7b947","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The dense glycocalyx of cancer cells can restrict immune-cell access to surface antigens and limit CAR-T cell activity. Here, we show that mucin density and epitope position determine how glycocalyx remodeling affects CAR-T cell recognition and killing. We identify KLK5 as a human protease that cleaves tumor-associated mucins, increases access to membrane-proximal antigens, and enhances CAR-T cell function. We then engineer CAR-T cells to display or secrete KLK5, enabling remodeling of the tumor glycocalyx during antigen recognition. KLK5-engineered CAR-T cells improved tumor control across multiple xenograft models, and KLK5-secreting MUC17 CAR-T cells produced the strongest in vivo benefit, prolonging survival compared with conventional MUC17 CAR-T cells. These findings show that CAR-T cells can be engineered to breach the mucin-rich glycocalyx while preserving accessible target epitopes.<\/jats:p>","DOI":"10.64898\/2026.09.25.754490","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:05:23Z","timestamp":1790571923000},"source":"Crossref","is-referenced-by-count":0,"title":["Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2701-3114","authenticated-orcid":false,"given":"Sangwoo","family":"Park","sequence":"first","affiliation":[{"name":"Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Cellular Immunotherapy Program, Mass General Brigham Cancer Institute, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassidy 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