{"id":54438,"date":"2026-01-27T19:34:55","date_gmt":"2026-01-27T18:34:55","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/01\/27\/removal-of-interstitial-hyaluronan-facilitates-subcutaneous-administration-and-lymphatic-delivery-of-anti-ctla4-and-improves-antitumor-efficacy\/"},"modified":"2026-01-27T19:34:55","modified_gmt":"2026-01-27T18:34:55","slug":"removal-of-interstitial-hyaluronan-facilitates-subcutaneous-administration-and-lymphatic-delivery-of-anti-ctla4-and-improves-antitumor-efficacy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/01\/27\/removal-of-interstitial-hyaluronan-facilitates-subcutaneous-administration-and-lymphatic-delivery-of-anti-ctla4-and-improves-antitumor-efficacy\/","title":{"rendered":"Removal of Interstitial Hyaluronan Facilitates Subcutaneous Administration and Lymphatic Delivery of Anti-CTLA4 and Improves Antitumor Efficacy"},"content":{"rendered":"
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Cancer Immunol Res<\/b>. 2026 Jan 27:OF1-OF13. doi: 10.1158\/2326-6066.CIR-25-0256. Online ahead of print.<\/p>\n

ABSTRACT<\/b><\/p>\n

Subcutaneous administration is an increasingly patient-preferred, alternative route of administration for monoclonal antibodies (mAb). To overcome the dose-volume restriction with subcutaneous administration and enable the large mAb doses typically required for immunotherapy, recombinant human hyaluronidase PH20 is co-dosed to transiently depolymerize hyaluronan at the injection site. Despite increasing clinical approvals and clinical trials of combination products with PH20, the potential impact of PH20 in facilitating intravenous-to-subcutaneous dose switching is largely unknown. In this study, we investigated whether increased lymphatic drainage via subcutaneous administration with PH20 co-dosing could improve the efficacy of anti-CTLA4 (\u03b1CTLA4) by increasing mAb access to the site of antitumor immunomodulation at the tumor-draining lymph node (TDLN). We showed that subcutaneous administration with PH20 significantly enhanced TDLN exposure of \u03b1CTLA4. In murine tumor models (CT26\/HAS or MC38\/OVA), this translated to improved tumor control compared with intravenous, and was either more efficacious or noninferior to subcutaneous alone. Greater efficacy occurred concomitantly with increased cytotoxic effector CD8+ T cells in the tumor and CD62L+ stem-like CD8+ T cells in the TDLN. This was due to increased mAb access to CTLA4+ T-cell populations at the TDLN and was only preserved at a lower mAb dose after subcutaneous administration with PH20. The efficacy advantage of subcutaneous administration with PH20 was primarily apparent for TDLN-targeted mAb (\u03b1CTLA4), as combination therapy with a non-TDLN-targeted mAb (\u03b1TIM3) was similarly efficacious regardless of dose routes. Overall, our study highlights the potential utility of PH20 to improve TDLN-targeted immunotherapy.<\/p>\n

PMID:41589716<\/a> | DOI:10.1158\/2326-6066.CIR-25-0256<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

Cancer Immunol Res. 2026 Jan 27:OF1-OF13. doi: 10.1158\/2326-6066.CIR-25-0256. Online ahead of print. ABSTRACT Subcutaneous administration is an increasingly patient-preferred, alternative route of administration for monoclonal antibodies (mAb). To overcome the dose-volume restriction with subcutaneous administration and enable the large mAb doses typically required for immunotherapy, recombinant human hyaluronidase PH20 is co-dosed to transiently depolymerize hyaluronan … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-54438","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/54438","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=54438"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/54438\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=54438"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=54438"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=54438"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}