Clinical and Immunologic Results of a Randomized Phase II Trial of Vaccination Using Four Melanoma Peptides Either Administered in Granulocyte-Macrophage Colony-Stimulating Factor in Adjuvant or Pulsed on Dendritic Cells

• DOI: 10.1200/jco.2003.10.005
• Publication Date: 2003-10-28T07:43:52Z
• Authors: Craig L. Slingluff; Gina R. Petroni; Galina V. Yamshch...; Donna L. Barnd; Shannon Eastham; Holly Galavotti; James W. Patterson; Donna H. Deacon; Sarah Hibbitts; David Teates; Patrice Y. Neese; William W. Grosh; Kimberly A. Chian...; Elizabeth M.H. Wo...; Catherine J. Wier...; Priscilla Merrill; Jennifer Gibson; Maureen Ross; Victor H. Engelhard
• Keywords: Adult; Male; Membrane Glycoproteins; Monophenol Monooxygenase; Granulocyte-Macrophage Colony-Stimulating Factor; Oleic Acids; Dendritic Cells; Middle Aged; Cancer Vaccines; Drug Administration Schedule; Peptide Fragments; Neoplasm Proteins; 3. Good health; Radiography; 03 medical and health sciences; 0302 clinical medicine; Humans; Interleukin-2; Female; Mannitol; Lymph Nodes; Melanoma; Aged

Purpose: To determine clinical and immunologic responses to a multipeptide melanoma vaccine regimen, a randomized phase II trial was performed.Patients and Methods: Twenty-six patients with advanced melanoma were randomly assigned to vaccination with a mixture of four gp100 and tyrosinase peptides restricted by HLA-A1, HLA-A2, and HLA-A3, plus a tetanus helper peptide, either in an emulsion with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Montanide ISA-51 adjuvant (Seppic Inc, Fairfield, NJ), or pulsed on monocyte-derived dendritic cells (DCs). Systemic low-dose interleukin-2 (Chiron, Emeryville, CA) was given to both groups. T-lymphocyte responses were assessed, by interferon gamma ELIspot assay (Chiron, Emeryville, CA), in peripheral-blood lymphocytes (PBLs) and in a lymph node draining a vaccine site (sentinel immunized node [SIN]).Results: In patients vaccinated with GM-CSF in adjuvant, T-cell responses to melanoma peptides were observed in 42% of PBLs and 80% of SINs, but in patients vaccinated with DCs, they were observed in only 11% and 13%, respectively. The overall immune response was greater in the GM-CSF arm (P < .02). Vitiligo developed in two of 13 patients in the GM-CSF arm but in no patients in the DC arm. Helper T-cell responses to the tetanus peptide were detected in PBLs after vaccination and correlated with T-cell reactivity to the melanoma peptides. Objective clinical responses were observed in two patients in the GM-CSF arm and one patient in the DC arm. Stable disease was observed in two patients in the GM-CSF arm and one patient in the DC arm.Conclusion: The high frequency of cytotoxic T-lymphocyte responses and the occurrence of clinical tumor regressions support continued investigation of multipeptide vaccines administered with GM-CSF in adjuvant.