{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:16:42Z","timestamp":1779909402400,"version":"3.53.1"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["242300421574"],"award-info":[{"award-number":["242300421574"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["2022M711060"],"award-info":[{"award-number":["2022M711060"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["30501346"],"award-info":[{"award-number":["30501346"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["242300421574"],"award-info":[{"award-number":["242300421574"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M711060"],"award-info":[{"award-number":["2022M711060"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["30501346"],"award-info":[{"award-number":["30501346"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Special Fund for Young Talents in Henan Agricultural University","award":["242300421574"],"award-info":[{"award-number":["242300421574"]}]},{"name":"Special Fund for Young Talents in Henan Agricultural University","award":["2022M711060"],"award-info":[{"award-number":["2022M711060"]}]},{"name":"Special Fund for Young Talents in Henan Agricultural University","award":["30501346"],"award-info":[{"award-number":["30501346"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Dendritic cell-cytokine-induced killer (DC-CIK) therapy faces limitations due to antigenic heterogeneity and suboptimal immune activation. In this study, we developed a multi-antigen-loaded DC-CIK (Ag-DC-CIK) system that co-targets Wilms\u2019 tumor 1 (WT1), mucin-1 (MUC1), and the TLR3 agonist poly(I:C) to improve therapeutic outcomes. Utilizing umbilical cord blood-derived DC and CIK cells, we demonstrated that Ag-DC-CIK significantly enhanced cytotoxicity, as evidenced by the lactate dehydrogenase (LDH) assay, and increased apoptosis induction, indicated by elevated Bax and reduced Bcl-2 expression, in various tumor cell lines (HeLa, HCT116, MKN45) and organoids generated from a gastric cancer patient. Furthermore, Ag-DC-CIK effectively suppressed tumor cell migration and reduced the viability of the organoid. In MKN45 xenograft models, Ag-DC-CIK treatment inhibited tumor growth without inducing systemic toxicity, as shown by decreased Ki67 cell proliferation. This tripartite strategy synergistically enhances DC-CIK therapy by expanding antigen recognition and augmenting immune responses, presenting a promising translational approach for the treatment of gastric cancer.<\/jats:p>","DOI":"10.3390\/biom15101356","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T12:15:31Z","timestamp":1758716131000},"page":"1356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dendritic Cell-Cytokine-Induced Killer Cells Co-Loaded with WT1\/MUC1\/Poly(I:C) Enhance Antitumor Immune Responses In Vitro and In Vivo"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-3799","authenticated-orcid":false,"given":"Huimin","family":"Liu","sequence":"first","affiliation":[{"name":"College of Life Sciences, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Chang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailing","family":"Tong","sequence":"additional","affiliation":[{"name":"Biocomer Technology Co., Ltd., Xiamen 361011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Mao","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hato, L., Vizcay, A., Eguren, I., P\u00e9rez-Gracia, J.L., Rodr\u00edguez, J., G\u00e1llego P\u00e9rez-Larraya, J., Sarobe, P., Inog\u00e9s, S., D\u00edaz de Cerio, A.L., and Santisteban, M. (2024). Dendritic Cells in Cancer Immunology and Immunotherapy. Cancers, 16.","DOI":"10.3390\/cancers16050981"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1517\/14712598.2014.900537","article-title":"An update on new adoptive immunotherapy strategies for solid tumors with cytokine-induced killer cells","volume":"14","year":"2014","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Garofano, F., Gonzalez-Carmona, M.A., Skowasch, D., Schmidt-Wolf, R., Abramian, A., Hauser, S., Strassburg, C.P., and Schmidt-Wolf, I.G.H. (2019). Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174307"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1186\/s13287-024-03869-z","article-title":"Cytokine-induced killer cells: New insights for therapy of hematologic malignancies","volume":"15","author":"Mehdizadeh","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1186\/s12967-024-05940-y","article-title":"Combined immunotherapy with dendritic cells and cytokine-induced killer cells for solid tumors: A systematic review and meta-analysis of randomized controlled trials","volume":"22","author":"Jiang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10984","DOI":"10.1073\/pnas.89.22.10984","article-title":"Human platelet-derived growth factor A chain is transcriptionally repressed by the Wilms tumor suppressor WT1","volume":"89","author":"Gashler","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21271","DOI":"10.1016\/S0021-9258(19)36920-0","article-title":"Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms\u2019 tumor locus","volume":"268","author":"Harrington","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/j.1349-7006.2004.tb02490.x","article-title":"Overexpression of the Wilms\u2019 tumor gene WT1 in pancreatic ductal adenocarcinoma","volume":"95","author":"Oji","year":"2004","journal-title":"Cancer Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.4049\/jimmunol.164.4.1873","article-title":"Cancer immunotherapy targeting Wilms\u2019 tumor gene WT1 product","volume":"164","author":"Oka","year":"2000","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/pbc.25792","article-title":"Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children","volume":"63","author":"Sawada","year":"2016","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1634\/theoncologist.2011-0240","article-title":"Active specific immunotherapy targeting the Wilms\u2019 tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: Lessons from early clinical trials","volume":"17","author":"Berneman","year":"2012","journal-title":"Oncologist"},{"key":"ref_12","first-page":"107","article-title":"Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen in pancreatic tumors","volume":"24","author":"Yamasaki","year":"2004","journal-title":"Int. J. Oncol."},{"key":"ref_13","first-page":"6846","article-title":"The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes","volume":"61","author":"Brossart","year":"2001","journal-title":"Cancer Res."},{"key":"ref_14","first-page":"398","article-title":"MUC1 overexpression is the most reliable marker of invasive carcinoma in intraductal papillary-mucinous tumor (IPMT)","volume":"52","author":"Ueda","year":"2005","journal-title":"Hepatogastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Apost\u00f3lico, J.S., Lunardelli, V.A.S., Yamamoto, M.M., Cunha-Neto, E., Boscardin, S.B., and Rosa, D.S. (2019). Poly(I:C) Potentiates T Cell Immunity to a Dendritic Cell Targeted HIV-Multiepitope Vaccine. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00843"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.4049\/jimmunol.1402228","article-title":"The combination of ISCOMATRIX adjuvant and TLR agonists induces regression of established solid tumors in vivo","volume":"194","author":"Silva","year":"2015","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.stem.2018.09.016","article-title":"A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening","volume":"23","author":"Yan","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbcan.2017.03.004","article-title":"Brain metastasization of breast cancer","volume":"1868","author":"Videira","year":"2017","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41523-020-00183-8","article-title":"Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells","volume":"6","author":"Muscarella","year":"2020","journal-title":"NPJ Breast Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.canlet.2013.09.016","article-title":"A personalized view on cancer immunotherapy","volume":"352","author":"Wayteck","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/hon.886","article-title":"Immunotherapy with cytokine induced killer cells in solid and hematopoietic tumours: A pilot clinical trial","volume":"27","author":"Olioso","year":"2009","journal-title":"Hematol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e12230","DOI":"10.1097\/MD.0000000000012230","article-title":"Cytokine-induced killer cell\/dendritic cell-cytokine-induced killer cell immunotherapy for the postoperative treatment of gastric cancer: A systematic review and meta-analysis","volume":"97","author":"Wang","year":"2018","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gao, D., Li, C., Xie, X., Zhao, P., Wei, X., Sun, W., Liu, H.C., Alexandrou, A.T., Jones, J., and Zhao, R. (2014). Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093886"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1007\/s12094-013-1001-9","article-title":"Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: Reargument of such contentious therapeutic preferences","volume":"15","author":"Ren","year":"2013","journal-title":"Clin. Transl. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Seya, T., Shingai, M., Kawakita, T., and Matsumoto, M. (2023). Two Modes of Th1 Polarization Induced by Dendritic-Cell-Priming Adjuvant in Vaccination. Cells, 12.","DOI":"10.3390\/cells12111504"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.ijbiomac.2018.02.034","article-title":"Poly(I:C) enhanced anti-cervical cancer immunities induced by dendritic cells-derived exosomes","volume":"113","author":"Chen","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1053\/j.gastro.2014.09.042","article-title":"In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection","volume":"148","author":"Bartfeld","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1111\/jgh.15930","article-title":"Patient-derived cancer organoids for drug screening: Basic technology and clinical application","volume":"37","author":"Ren","year":"2022","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13308","DOI":"10.1073\/pnas.1516689112","article-title":"Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases","volume":"112","author":"Weeber","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1356\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:55Z","timestamp":1760035735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":29,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["biom15101356"],"URL":"https:\/\/doi.org\/10.3390\/biom15101356","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}