title: Re-inventing intratumoral immunotherapy for melanoma.
abstract: Immunotherapeutics have been applied intratumorally to manage accessible lesions and to induce systemic immunity in malignant melanoma. Intratumoral bacillus Calmette-Guérin (BCG) has been used for 40 years, and intratumoral BCG, IL-2, IFN-α and imiquimod are recommended as treatment options for patients with in-transit melanoma metastases. Regression of cutaneous metastases can be achieved. Subcutaneous metastases are more refractory, and regression of uninjected, visceral metastases is infrequent. Other microbial products, cytokines, chemicals, immune cells, antibody and viral and plasmid vectors expressing immunologically active molecules have been tested. Antitumor activity has not been demonstrated to be superior to that of intratumoral BCG. There are few controlled trials, and whether survival is impacted with any approach has not yet been established. The immunotherapeutics applied and the intratumoral administration procedure itself can activate responses that are immune inhibitory. More rigorous clinical testing and improved understanding and modulation of regulatory immune responses are necessary.
authors.affiliation: Melanoma Program, The Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA. triozzp@ccf.org
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Tuthill
authors.forename: Ernest
authors.initials: E
authors.lastname: Borden
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D000077271:Imiquimod; D007167:Immunotherapy / Q000379:methods*; D015552:Injections, Intralesional; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D001500:BCG Vaccine; D016207:Cytokines; D000077271:Imiquimod