6533b85efe1ef96bd12c0973
RESEARCH PRODUCT
Ultrasound-guided intra-tumor injection of combined immunotherapy cures mice from orthotopic prostate cancer.
Mario P. ColomboClaudia ChiodoniIvano ArioliClaudio TripodoGiorgio MauriMariella Parenzasubject
MaleCancer ResearchPathologymedicine.medical_specialtyStromal cellmedicine.medical_treatmentImmunologyFluorescent Antibody TechniqueGene deliveryCD8-Positive T-LymphocytesInjections Intralesionalprostate cancer;immunotherapyAdenoviridaeImmunoenzyme TechniquesProstate cancerMiceTumor Cells CulturedImmunology and AllergyMedicineAnimalsHumansCell ProliferationUltrasonographyTumor microenvironmentbusiness.industryAntibodies MonoclonalProstatic NeoplasmsImmunotherapyT lymphocyteGenetic Therapyprostate cancermedicine.diseaseCombined Modality TherapyInterleukin-10Mice Inbred C57BLOncologyOligodeoxyribonucleotidesChemokines CCSystemic administrationImmunotherapybusinessCD8description
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.
year | journal | country | edition | language |
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2013-01-01 | Cancer immunology, immunotherapy : CII |