{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:38:40Z","timestamp":1780637920604,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tumor\u2010targeted CD40 agonists have emerged as one of the novel strategies to activate intratumoral antigen\u2010presenting cells (APCs), subsequently inducing T\u2010cell\u2010specific antitumor responses. However, their clinical efficacy as monotherapy has been limited, highlighting the need for effective combination therapies. We developed KK2269, a bispecific antibody targeting epithelial cell adhesion molecule (EpCAM) on tumor cells and CD40 on APCs, designed to selectively activate APCs in the presence of EpCAM\u2010positive tumors. Our studies demonstrated that KK2269 activates APCs only in the presence of EpCAM\u2010expressing cells. Using the immunologically cold B16F10\u2010mouse EpCAM subcutaneously transplanted model, the antitumor effects of KK2269 in combination with clinically approved drugs, including anti\u2010programmed cell death 1 (PD\u20101) antibody, docetaxel, doxorubicin, oxaliplatin, and gemcitabine were evaluated. KK2269 showed significant antitumor activity in combination with an anti\u2010PD\u20101 antibody, docetaxel, doxorubicin, or oxaliplatin, but not gemcitabine, with docetaxel showing the most significant antitumor effect(s). Intratumoral immune analysis showed that KK2269 was associated with increased expression of APC activation markers, whereas docetaxel was associated with increased expression of dendritic cell (DC)\u2010related genes. Moreover, expression of APC and T\u2010cell activation markers was higher with docetaxel+KK2269 than with either monotherapy. The antitumor and immune activation effects of docetaxel+KK2269 were also observed in the immunosuppressive intrahepatic transplantation model. This study provides a rationale for combining a tumor\u2010targeting CD40 agonist, KK2269, with docetaxel for the treatment of PD\u20101 blockade resistant tumors, including intrahepatic tumors, and supports exploration of this combination strategy in the clinic.<\/jats:p>","DOI":"10.1111\/cas.70376","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T16:42:13Z","timestamp":1776357733000},"page":"1701-1712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Docetaxel\u2010Induced Immune Activation Shows Antitumor Synergy With the Tumor\u2010Targeted\n                    <scp>CD40<\/scp>\n                    Agonist\n                    <scp>KK2269<\/scp>"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9286-8116","authenticated-orcid":false,"given":"Yuta","family":"Tezuka","sequence":"first","affiliation":[{"name":"Research Division, Kyowa Kirin Co.  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