Ultrasound-guided intra-tumor injection of combined immunotherapy cures mice from orthotopic prostate cancer

• Published in: Cancer Immunology, Immunotherapy Vol. 62; no. 12; pp. 1811 - 1819
• Main Authors: Mauri, Giorgio, Chiodoni, Claudia, Parenza, Mariella, Arioli, Ivano, Tripodo, Claudio, Colombo, Mario Paolo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2013; Springer Nature B.V
• Subjects: Adenoviridae - genetics; Adenoviruses; Animals; Antibodies; Antibodies, Monoclonal - pharmacology; Cancer Research; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Chemokines; Chemokines, CC - genetics; Combined Modality Therapy; Cytokines; Fluorescent Antibody Technique; Genetic Therapy; Humans; Immunoenzyme Techniques; Immunology; Immunotherapy; Injections, Intralesional; Interleukin-10 - antagonists & inhibitors; Interleukin-10 - immunology; Interleukin-10 - metabolism; Leukocytes; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Oligodeoxyribonucleotides - genetics; Oncology; Original; Original Article; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - immunology; Prostatic Neoplasms - therapy; Transplants & implants; Tumor Cells, Cultured; Tumors; Ultrasonic imaging; Ultrasonography; Ultrasound-guided immunotherapy; Local cancer immunotherapy; Prostate tumor; Combination treatment; CpG oligonucleotides; CCL-16
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-013-1486-7

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.