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13.08.2016 | Original Article

Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases

verfasst von: Ileana S. Mauldin, Nolan A. Wages, Anne M. Stowman, Ena Wang, Walter C. Olson, Donna H. Deacon, Kelly T. Smith, Nadedja Galeassi, Jessica E. Teague, Mark E. Smolkin, Kimberly A. Chianese‐Bullock, Rachael A. Clark, Gina R. Petroni, Francesco M. Marincola, David W. Mullins, Craig L. Slingluff Jr.

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 10/2016

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Abstract

Introduction

Infiltration of cancers by T cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T cell infiltration of tumors are not known. This study was designed to assess whether topical treatment of melanoma metastases with the TLR7 agonist imiquimod plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases.

Patients and methods

Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to metastatic tumors daily. Adverse events were recorded, and effects on the tumor microenvironment were evaluated from sequential tumor biopsies. T cell responses were assessed by IFNγ ELIspot assay and T cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression.

Results and conclusions

Four eligible patients were enrolled, and administration of imiquimod and vaccination were well tolerated. Circulating T cell responses to the vaccine was detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma.

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Titel: Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases
verfasst von: Ileana S. Mauldin
Nolan A. Wages
Anne M. Stowman
Ena Wang
Walter C. Olson
Donna H. Deacon
Kelly T. Smith
Nadedja Galeassi
Jessica E. Teague
Mark E. Smolkin
Kimberly A. Chianese‐Bullock
Rachael A. Clark
Gina R. Petroni
Francesco M. Marincola
David W. Mullins
Craig L. Slingluff Jr.
Publikationsdatum: 13.08.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 10/2016
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1880-z

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Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases