title: Intratumoral Delivery of Immunotherapy-Act Locally, Think Globally.
abstract: Immune mechanisms have evolved to cope with local entry of microbes acting in a confined fashion but eventually inducing systemic immune memory. Indeed, in situ delivery of a number of agents into tumors can mimic in the malignant tissue the phenomena that control intracellular infection leading to the killing of infected cells. Vascular endothelium activation and lymphocyte attraction, together with dendritic cell-mediated cross-priming, are the key elements. Intratumoral therapy with pathogen-associated molecular patterns or recombinant viruses is being tested in the clinic. Cell therapies can be also delivered intratumorally, including infusion of autologous dendritic cells and even tumor-reactive T lymphocytes. Intralesional virotherapy with an HSV vector expressing GM-CSF has been recently approved by the Food and Drug Administration for the treatment of unresectable melanoma. Immunomodulatory monoclonal Abs have also been successfully applied intratumorally in animal models. Local delivery means less systemic toxicity while focusing the immune response on the malignancy and the affected draining lymph nodes.
authors.affiliation: Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.
authors.forename: M Angela
authors.initials: MA
authors.lastname: Aznar
authors.affiliation: Department of Experimental and Clinical Sciences, G. D'Annunzio University and Foundation, Chieti 66100, Italy.
authors.forename: Nicola
authors.identifier: 0000-0001-8449-5407
authors.initials: N
authors.lastname: Tinari
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona 08908, Spain; and.
authors.forename: Antonio J
authors.identifier: 0000-0002-7365-9629
authors.initials: AJ
authors.lastname: Rullán
authors.affiliation: Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.
authors.forename: Alfonso R
authors.initials: AR
authors.lastname: Sánchez-Paulete
authors.affiliation: Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.|University Clinic, University of Navarra and Health Research Institute of Navarra, 31008 Pamplona, Spain.
authors.forename: María E
authors.initials: ME
authors.lastname: Rodriguez-Ruiz
authors.affiliation: Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain; imelero@unav.es.|University Clinic, University of Navarra and Health Research Institute of Navarra, 31008 Pamplona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents