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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1201-1212
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume65
Issue number10
DOIs
Publication statusPublished - 1 Oct 2016

Fingerprint

imiquimod
Cancer Vaccines
Melanoma
Neoplasm Metastasis
T-Lymphocytes
Neoplasms
Therapeutics
Vaccines
Combined Vaccines
Peptides
Tetanus Toxoid
Tumor Microenvironment
Chemokines
Vaccination
Staining and Labeling
Cytokines
Biopsy

Keywords

  • Cytotoxic T lymphocytes
  • Human
  • Immunotherapy
  • Melanoma
  • TLR agonists
  • Tumor vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases. / Mauldin, Ileana S.; Wages, Nolan A.; Stowman, Anne M.; Wang, Ena; Olson, Walter C.; Deacon, Donna H.; Smith, Kelly T.; Galeassi, Nadedja; Teague, Jessica E.; Smolkin, Mark E.; Chianese‐Bullock, Kimberly A.; Clark, Rachael A.; Petroni, Gina R.; Marincola, Francesco M.; Mullins, David W.; Slingluff, Craig L.

In: Cancer Immunology, Immunotherapy, Vol. 65, No. 10, 01.10.2016, p. 1201-1212.

Research output: Contribution to journalArticle

Mauldin, IS, Wages, NA, Stowman, AM, Wang, E, Olson, WC, Deacon, DH, Smith, KT, Galeassi, N, Teague, JE, Smolkin, ME, Chianese‐Bullock, KA, Clark, RA, Petroni, GR, Marincola, FM, Mullins, DW & Slingluff, CL 2016, 'Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases', Cancer Immunology, Immunotherapy, vol. 65, no. 10, pp. 1201-1212. https://doi.org/10.1007/s00262-016-1880-z
Mauldin, Ileana S. ; Wages, Nolan A. ; Stowman, Anne M. ; Wang, Ena ; Olson, Walter C. ; Deacon, Donna H. ; Smith, Kelly T. ; Galeassi, Nadedja ; Teague, Jessica E. ; Smolkin, Mark E. ; Chianese‐Bullock, Kimberly A. ; Clark, Rachael A. ; Petroni, Gina R. ; Marincola, Francesco M. ; Mullins, David W. ; Slingluff, Craig L. / Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases. In: Cancer Immunology, Immunotherapy. 2016 ; Vol. 65, No. 10. pp. 1201-1212.
@article{11c4ae1405f8498b89e895d2066545ec,
title = "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.",
keywords = "Cytotoxic T lymphocytes, Human, Immunotherapy, Melanoma, TLR agonists, Tumor vaccines",
author = "Mauldin, {Ileana S.} and Wages, {Nolan A.} and Stowman, {Anne M.} and Ena Wang and Olson, {Walter C.} and Deacon, {Donna H.} and Smith, {Kelly T.} and Nadedja Galeassi and Teague, {Jessica E.} and Smolkin, {Mark E.} and Chianese‐Bullock, {Kimberly A.} and Clark, {Rachael A.} and Petroni, {Gina R.} and Marincola, {Francesco M.} and Mullins, {David W.} and Slingluff, {Craig L.}",
year = "2016",
month = "10",
day = "1",
doi = "10.1007/s00262-016-1880-z",
language = "English",
volume = "65",
pages = "1201--1212",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "10",

}

TY - JOUR

T1 - Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases

AU - Mauldin, Ileana S.

AU - Wages, Nolan A.

AU - Stowman, Anne M.

AU - Wang, Ena

AU - Olson, Walter C.

AU - Deacon, Donna H.

AU - Smith, Kelly T.

AU - Galeassi, Nadedja

AU - Teague, Jessica E.

AU - Smolkin, Mark E.

AU - Chianese‐Bullock, Kimberly A.

AU - Clark, Rachael A.

AU - Petroni, Gina R.

AU - Marincola, Francesco M.

AU - Mullins, David W.

AU - Slingluff, Craig L.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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.

KW - Cytotoxic T lymphocytes

KW - Human

KW - Immunotherapy

KW - Melanoma

KW - TLR agonists

KW - Tumor vaccines

UR - http://www.scopus.com/inward/record.url?scp=84982181873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84982181873&partnerID=8YFLogxK

U2 - 10.1007/s00262-016-1880-z

DO - 10.1007/s00262-016-1880-z

M3 - Article

VL - 65

SP - 1201

EP - 1212

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 10

ER -