{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:21:00Z","timestamp":1792092060366,"version":"4.4.0"},"reference-count":130,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council (NSTC), Taiwan","award":["110-2314-B-039-026-MY3-"],"award-info":[{"award-number":["110-2314-B-039-026-MY3-"]}]},{"name":"National Science and Technology Council (NSTC), Taiwan","award":["DMR-112-202"],"award-info":[{"award-number":["DMR-112-202"]}]},{"name":"National Science and Technology Council (NSTC), Taiwan","award":["DMR-CELL-1807"],"award-info":[{"award-number":["DMR-CELL-1807"]}]},{"name":"China Medical University Hospital (CMUH), Taiwan","award":["110-2314-B-039-026-MY3-"],"award-info":[{"award-number":["110-2314-B-039-026-MY3-"]}]},{"name":"China Medical University Hospital (CMUH), Taiwan","award":["DMR-112-202"],"award-info":[{"award-number":["DMR-112-202"]}]},{"name":"China Medical University Hospital (CMUH), Taiwan","award":["DMR-CELL-1807"],"award-info":[{"award-number":["DMR-CELL-1807"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Immunotherapy using systemic immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cells has revolutionized cancer treatment, but it only benefits a subset of patients. Systemic immunotherapies cause severe autoimmune toxicities and cytokine storms. Immune-related adverse events (irAEs) plus the immunosuppressive tumor microenvironment (TME) have been linked to the inefficacy of systemic immunotherapy. Intratumoral immunotherapy that increases immunotherapeutic agent bioavailability inside tumors could enhance the efficacy of immunotherapies and reduce systemic toxicities. In preclinical and clinical studies, intratumoral administration of immunostimulatory agents from small molecules to xenogeneic cells has demonstrated antitumor effects not only on the injected tumors but also against noninjected lesions. Herein, we review and discuss the results of these approaches in preclinical models and clinical trials to build the landscape of intratumoral immunotherapeutic agents and we describe how they stimulate the body\u2019s immune system to trigger antitumor immunity as well as the challenges in clinical practice. Systemic and intratumoral combination immunotherapy would make the best use of the body\u2019s immune system to treat cancers. Combining precision medicine and immunotherapy in cancer treatment would treat both the mutated targets in tumors and the weakened body\u2019s immune system simultaneously, exerting maximum effects of the medical intervention.<\/jats:p>","DOI":"10.3390\/vaccines11111717","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T11:03:45Z","timestamp":1699959825000},"page":"1717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Immunotherapeutic Agents for Intratumoral Immunotherapy"],"prefix":"10.3390","volume":"11","author":[{"given":"Chih-Rong","family":"Shyr","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404328, Taiwan"},{"name":"eXCELL Biotherapeutics Inc., Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang-Chi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Department of Surgery, College of Medicine, China Medical University and Hospital, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Shan","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Ping","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Urology Division, China Medical University and Hospital, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/annonc\/mdw604","article-title":"Causes of death among cancer patients","volume":"28","author":"Zaorsky","year":"2017","journal-title":"Ann. 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