{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:36:17Z","timestamp":1785418577794,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007185","name":"UCLA","doi-asserted-by":"publisher","award":["UCLA2204"],"award-info":[{"award-number":["UCLA2204"]}],"id":[{"id":"10.13039\/100007185","id-type":"DOI","asserted-by":"publisher"}]},{"award":["UCLA2204"],"award-info":[{"award-number":["UCLA2204"]}],"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Systemic administration of antibodies that target immune checkpoint inhibitor pathways is a highly effective approach to cancer immunotherapy, but systemic toxicity can limit clinical utility. In preclinical testing, a peri-tumor injection of a low dose of hydrogel-encapsulated cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody was shown to selectively activate T cells in tumor-draining lymph nodes, induce tumor infiltration by cytotoxic T cells, and result in tumor regression, protective immunity, and long-term survival. In contrast to systemic therapy, there was limited systemic exposure or risk for autoimmune toxicity. The current study focuses on translating this platform into a biocompatible human therapeutic. The hydrogel matrix was reformulated using a low-molecular-weight hyaluronic acid. A recombinant human hyaluronidase (rHuPH20) was incorporated to promote lymph node targeting and self-resorbing features. Formulations were optimized to operate at neutral pH and with gelation kinetics allowing a 5 to 10 min administration window. Performance features were assessed including the capacity to encapsulate human IgG or ipilimumab antibody at proposed therapeutic doses (1\u201315 mg\/mL), impact of rHuPH20 and antibody on rheologic properties and three-dimensional microstructure, and payload delivery profiles in vitro and in vivo. Results confirm the capacity for this unique hydrogel platform to be adapted for human testing.<\/jats:p>","DOI":"10.3390\/gels12060489","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Translating a Preclinical Hydrogel Platform into a Human Therapeutic for Delivering Targeted Low-Dose Anti-CTLA-4"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5730-4035","authenticated-orcid":false,"given":"Airi","family":"Harui","sequence":"first","affiliation":[{"name":"Division of Pulmonary & Critical Care, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1690, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-6578","authenticated-orcid":false,"given":"Michael D.","family":"Roth","sequence":"additional","affiliation":[{"name":"Division of Pulmonary & Critical Care, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1690, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1600-065X.2008.00662.x","article-title":"Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways","volume":"224","author":"Fife","year":"2008","journal-title":"Immunol. 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