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

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.

• Authors: 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
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 65 Issue 10 Pg. 1201-12 (10 2016) ISSN: 1432-0851 [Electronic] Germany
• PMID: 27522582 (Publication Type: Journal Article)

Chemical References

• Aminoquinolines
• Antigens, Neoplasm
• Antineoplastic Agents
• Cancer Vaccines
• Cytokines
• Peptide Fragments
• TLR7 protein, human
• Toll-Like Receptor 7
• Vaccines, Subunit
• Imiquimod

Topics

• Administration, Topical
• Aged
• Aminoquinolines (therapeutic use)
• Antigens, Neoplasm (immunology)
• Antineoplastic Agents (therapeutic use)
• Cancer Vaccines (immunology)
• Cell Movement (drug effects)
• Cells, Cultured
• Combined Modality Therapy
• Cytokines (genetics, metabolism)
• Enzyme-Linked Immunospot Assay
• Female
• Humans
• Imiquimod
• Lymphocytes, Tumor-Infiltrating (pathology)
• Male
• Melanoma (secondary, therapy)
• Middle Aged
• Neoplasm Staging
• Peptide Fragments (immunology)
• Skin Neoplasms (secondary, therapy)
• T-Lymphocytes (drug effects, immunology)
• Toll-Like Receptor 7 (agonists)
• Transcriptome (immunology)
• Vaccines, Subunit (immunology)