title: Armed antibodies for cancer treatment: a promising tool in a changing era.
abstract: Advances in the understanding of tumor immunology and molecular biology of melanoma cells have favored a larger application of immunotherapy and targeted therapies in the clinic. Several selective mutant gene inhibitors and immunomodulating antibodies have been reported to improve overall survival or progression-free survival in metastatic melanoma patients. However, despite impressive initial responses, patients treated with selective inhibitors relapse quickly, and toxicities associated to the use of immunomodulating antibodies are not easily manageable. In this sense, the concept of using antibodies as delivery vehicles for the preferential in vivo localization of the drug at the site of disease with reduction of side effects has raised particular interest. Antibody-cytokine fusion proteins (termed immunocytokines) represent a new simple and effective way to deliver the immunomodulatory payload at the tumor site, with the aim of inducing both local and systemic antitumoral immune responses and limiting systemic toxicities. Several clinical trials have been conducted and are actually ongoing with different immunocytokines, in several tumor histotypes. In metastatic melanoma patients, different drug delivery modalities such as systemic, loco-regional and intratumoral are under investigation. In this review, the rationale for the use of L19-IL2 and L19-TNF, two clinical stage immunocytokines produced by the Philogen group, as well as opportunities for their future development will be discussed.
authors.affiliation: Medical Oncology and Immunotherapy, Azienda Ospedaliera Universitaria Senese, Istituto Toscano Tumori, University Hospital of Siena, Strada delle Scotte, 53100, Siena, Italy, riccardo.danielli@ao-siena.toscana.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Danielli
authors.forename: Roberto
authors.initials: R
authors.lastname: Patuzzo
authors.forename: Pier Adelchi
authors.initials: PA
authors.lastname: Ruffini
authors.forename: Andrea
authors.initials: A
authors.lastname: Maurichi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Giovannoni
authors.forename: Giuliano
authors.initials: G
authors.lastname: Elia
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D011993:Recombinant Fusion Proteins