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These approaches deliver concentrated doses of therapeutic immune agents directly into individual tumor(s), achieving local tumor control and induction of systemic antitumor immune responses while minimizing the risk of immune\u2010related adverse events. Talimogene laherparepvec, a genetically modified herpes simplex virus type 1\u2013encoding granulocyte\u2010macrophage colony\u2013stimulating factor, was the first oncolytic viral therapy approved in a solid tumor indication. In pivotal trials of patients with melanoma, talimogene laherparepvec demonstrated durable responses. Building on this paradigm, next\u2010generation oncolytic agents incorporate additional genetic modifications, such as fusogenic proteins and immunostimulatory transgenes, to enhance local cytotoxicity and systemic immune priming. Clinical studies of intratumoral, injectable agents since 2010 have evaluated monotherapy as well as combination strategies with immune checkpoint inhibitors, revealing improved response rates and durable remissions, including in patients with immune checkpoint inhibitor\u2010resistant disease. This review summarizes the mechanistic rationale, preclinical evidence, and clinical development of intratumoral therapies in melanoma. Key trial outcomes, safety profiles, and practical considerations for administration are discussed. Emerging trends include image\u2010guided visceral injection, combinatorial regimens, and the integration of intratumoral therapy in the neoadjuvant setting. As these therapies evolve, intratumoral approaches may expand their role in melanoma management, bridging locoregional tumor control with systemic immune activation and complementing existing systemic treatments.<\/jats:p>","DOI":"10.1002\/cncr.70400","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T22:42:01Z","timestamp":1782427321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Updates on intratumoral therapies in melanoma"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8417-2787","authenticated-orcid":false,"given":"Vincent T.","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Dermatology University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"HonorHealth Research Institute  Scottsdale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa K.","family":"Steimle","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janmesh D.","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Dermatology University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Burkey","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4427-9387","authenticated-orcid":false,"given":"Justin C.","family":"Moser","sequence":"additional","affiliation":[{"name":"HonorHealth Research Institute  Scottsdale Arizona USA"},{"name":"Arizona State University School of Medicine and Advanced Medical Engineering  Scottsdale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad","family":"Javed","sequence":"additional","affiliation":[{"name":"University of Chicago Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hibba","family":"tul Rehman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Ege","family":"Seker","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Birbrair","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orhan S.","family":"Ozkan","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Albertini","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Dermatology University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Medical Service William S. 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