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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.

Original publication

DOI

10.4049/jimmunol.1601145

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

01/2017

Volume

198

Pages

31 - 39

Addresses

Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.

Keywords

Animals, Humans, Neoplasms, Antineoplastic Agents, Immunotherapy