title: Ultrasound-guided intra-tumor injection of combined immunotherapy cures mice from orthotopic prostate cancer.
abstract: Intra-tumor injection of immunotherapeutic agents is often the most effective, likely because of concomitant modification of tumor microenvironment. We tested an immunotherapeutic regimen consisting of CpG oligonucleotides and of adenovirus-mediated gene delivery of CCL16 chemokine directly into orthotopically implanted prostate tumors by ultrasound-guided injection, followed by systemic administration of an anti-IL-10R antibody. This combination treatment induced rapid stromal rearrangement, characterized by massive leukocyte infiltration and large areas of necrosis, a scenario that eventually led to complete tumor rejection and systemic immunity in 75 % of the treated mice. In vivo T lymphocyte depletion experiments demonstrated that the efficacy of CCL16/CpG/anti-IL-10R combination treatment relies upon CD8 T lymphocytes whereas CD4 T cells are dispensable. The results underlie the feasibility of echo-guided local immunotherapy of tumors located in visceral organs that are not easily accessible.
authors.affiliation: Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mauri
authors.forename: Claudia
authors.initials: C
authors.lastname: Chiodoni
authors.forename: Mariella
authors.initials: M
authors.lastname: Parenza
authors.forename: Ivano
authors.initials: I
authors.lastname: Arioli
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Mario Paolo
authors.initials: MP
authors.lastname: Colombo
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D019742:Chemokines, CC / Q000235:genetics*; D003131:Combined Modality Therapy; D005455:Fluorescent Antibody Technique; D015316:Genetic Therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D015552:Injections, Intralesional; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D014463:Ultrasonography
chemical_list: D000911:Antibodies, Monoclonal; C481939:CCL16 protein, human; C408982:CPG-oligonucleotide; D019742:Chemokines, CC; D009838:Oligodeoxyribonucleotides; D016753:Interleukin-10