Combined intratumoral regulatory T-cell depletion and transforming growth factor-β neutralization induces regression of established AE17 murine mesothelioma tumors.
Suppression of an anti-tumor immune response by regulatory T cells (T(regs)) in tumor-bearing hosts is now well established. Previously, we have reported that the intratumoral administration of T(reg)-depleting anti-CD25 monoclonal antibody every 10 days is highly effective at inhibiting the further development of established murine mesotheliomas. Here we investigate the dosage, kinetics, and immunology of this treatment. Further, we show that by precisely timing neutralization of transforming growth factor-β (TGF-β) within treated tumors using a TGF-β-soluble receptor, the efficacy of the treatment can be significantly improved, resulting in tumor regression. We suggest that this combined intratumoral treatment approach can be applied clinically for the treatment of mesothelioma.
Kissick
Haydn T
HT
Discipline of Microbiology and Immunology, School of Biomedical, Biomolecular, and Chemical Sciences, University of Western Australia, Crawley, Western Australia, Australia.
Ireland
Demelza J
DJ
Beilharz
Manfred W
MW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D008654:Mesothelioma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016212:Transforming Growth Factor beta