{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:27:45Z","timestamp":1786548465613,"version":"build-2736575974"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tavotek Biotherapeutics, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cadherin-17 (CDH17) is a cell-adhesion molecule physiologically expressed along the intestinal epithelial tight junctions. Aberrant overexpression of CDH17 in gastrointestinal (GI) cancers promotes tumor growth and metastasis and is associated with poor patient prognosis. Due to its restricted expression in normal tissues and strong association with malignancy, CDH17 represents an emerging therapeutic target for GI tract cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A high-affinity anti-CDH17 monoclonal antibody (TAVO307) was generated and conjugated with auristatin-derived cytotoxic payloads to obtain CDH17-directed antibody\u2013drug conjugates (ADCs). In parallel, a VHH antibody capable of activating \u03b3\u03b4 T cell receptors from both V\u03b41 and V\u03b42 subsets was identified and combined with the anti-CDH17 antibody to generate CDH17-targeted T cell engager (TCE) to recruit \u03b3\u03b4 T cells, which are abundant in the intestinal mucosa and play a critical role in tumor immunosurveillance. An attenuated interleukin-15 (IL-15) fused with the IL-15 receptor \u03b1 sushi domain was further incorporated on TCE to enhance \u03b3\u03b4 T cell expansion and activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CDH17-based ADCs exhibited potent and selective cytotoxicity in multiple GI cancer cell lines and significant tumor regression in xenograft models. The CDH17 \u03b3\u03b4 TCE induced tumor antigen-dependent \u03b3\u03b4 T cell degranulation and redirected both V\u03b41 and V\u03b42 T cells to effectively kill CDH17-expressing cancer cells. IL-15 fusion further augmented \u03b3\u03b4 T cell expansion and activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Both CDH17-targeted ADCs and \u03b3\u03b4 TCEs demonstrated promising potency and efficacy to control GI cancers. They could offer complementary therapeutic options that could be used in combination therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/abt\/tbag012","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:38:44Z","timestamp":1773329924000},"page":"230-247","source":"Crossref","is-referenced-by-count":0,"title":["Novel ADC and \u03b3\u03b4 T cell engager targeting CDH17 for the therapy of gastrointestinal cancers"],"prefix":"10.1093","volume":"9","author":[{"given":"Mingcan","family":"Yu","sequence":"first","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Ambler, PA 19002 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmao","family":"Mu","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Suzhou , 215000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Suzhou , 215000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglei","family":"Bi","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Suzhou , 215000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Suzhou , 215000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxia","family":"Zha","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Suzhou , 215000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Suzhou , 215000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Suzhou , 215000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jin","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Suzhou , 215000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanting","family":"Chen","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Ambler, PA 19002 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L","family":"Chiu","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Ambler, PA 19002 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1147-9444","authenticated-orcid":false,"given":"Di","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tavotek Biotherapeutics Inc ., Ambler, PA 19002 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"2026081210212118300_ref1","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/j.1749-6632.2000.tb05236.x","article-title":"Intestinal cell adhesion molecules. 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