Pilot study of granulocyte-macrophage colony-stimulating factor and interleukin-2 as immune adjuvants for a melanoma peptide vaccine

Matthew S Block, Vera Jean Suman, Wendy K. Nevala, Lisa A. Kottschade, Edward T. Creagan, Judith S Kaur, Jorge Fernando Quevedo, Robert R Mc Williams, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Thus far, peptide vaccines used to stimulate tumor-specific immune responses in patients with melanoma have been largely unsuccessful. Granulocyte-macrophage colony-stimulating factor and interleukin-2 are immune-potentiating cytokines that have improved vaccine responses in preclinical models. We hypothesized that higher doses of granulocyte-macrophage colony-stimulating factor and addition of low-dose interleukin-2 might augment responses to vaccine antigens. Patients with resected stage II, III, or IV melanoma were treated with vaccines containing three melanoma-associated peptides [MART-1a, gp100(207-217), and survivin], along with 300 or 500 mcg granulocyte-macrophage colony-stimulating factor in Montanide ISA. Cohorts of patients received low-dose subcutaneous interleukin-2 on days 7-20 after vaccination. Induction of a response was defined as either doubling of cytotoxic T lymphocyte frequency from baseline or increase in frequency from undetectable (<0.05%) to detectable. Leukocyte subsets and plasma cytokines were analyzed before and after vaccination. Cytotoxic T lymphocyte responses to MART-1a, gp100(207-217), and survivin were induced in 11, 16, and 14 of 19 patients, respectively. Responses were not higher in patients receiving 500 mcg granulocyte-macrophage colony-stimulating factor or low-dose interleukin-2 than in patients receiving 300 mcg granulocyte-macrophage colony-stimulating factor only. Interleukin-2 treatment (in nine patients) led to increases in natural killer cells and T regulatory cells compared with no interleukin-2 treatment (nine patients). Multiple plasma cytokines were transiently induced during vaccination. Neither increasing the dose of granulocyte-macrophage colony-stimulating factor nor addition of low-dose interleukin-2 resulted in an increase in the frequency of vaccine-specific cytotoxic T lymphocytes to a melanoma peptide vaccine. The increase in T regulatory cells associated with interleukin-2 treatment suggests that interleukin-2 may be immunosuppressive in this setting.

Original languageEnglish (US)
Pages (from-to)438-445
Number of pages8
JournalMelanoma Research
Volume21
Issue number5
DOIs
StatePublished - Oct 2011

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Subunit Vaccines
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-2
Melanoma
Cytotoxic T-Lymphocytes
Vaccines
Vaccination
Cytokines
Natural Killer T-Cells
Regulatory T-Lymphocytes
Immunosuppressive Agents
Leukocytes
Therapeutics
Antigens
Peptides

Keywords

  • cancer vaccine
  • cytokines
  • granulocyte-macrophage colony-stimulating factor
  • interleukin-2
  • melanoma
  • phase I clinical trial

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Dermatology

Cite this

Pilot study of granulocyte-macrophage colony-stimulating factor and interleukin-2 as immune adjuvants for a melanoma peptide vaccine. / Block, Matthew S; Suman, Vera Jean; Nevala, Wendy K.; Kottschade, Lisa A.; Creagan, Edward T.; Kaur, Judith S; Quevedo, Jorge Fernando; Mc Williams, Robert R; Markovic, Svetomir Nenad.

In: Melanoma Research, Vol. 21, No. 5, 10.2011, p. 438-445.

Research output: Contribution to journalArticle

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