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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

Craig L. Slingluff, Jr, Gina R. Petroni, Galina V. Yamshchikov, 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. Chianese-Bullock, Elizabeth M.H. Woodson, Catherine J. Wiernasz, Priscilla Merrill, Jennifer Gibson, Maureen Ross, Victor H. Engelhard

From the Department of Surgery/Division of Surgical Oncology, Departments of Health Evaluation Sciences, Pathology, Radiology, Medicine/Division of Hematology-Oncology, and Microbiology/Beirne Carter Center for Immunology, Cancer Center Clinical Trials Office, University of Virginia, Charlottesville, VA.

Address reprint requests to Craig L. Slingluff Jr, Department of Surgery, Human Immune Therapy Center, University of Virginia, 1352 Jordan Hall, PO Box 801457, Charlottesville, VA 22908; e-mail: cls8h{at}virginia.edu.

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.

Supported in part by National Institutes of Health grant R01 CA78519 and the Cancer Research Institute (C.L.S.); Schering-Plough Research Institute; Argonex Inc; Chiron Corporation; and the Human Immune Therapy Center, the Cancer Center Support Grant (National Institutes of Health grant P30CA44579), the Pratt Fund, and the General Clinical Research Center (grant M01 RR00847) at the University of Virginia.

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• Maturation Matters: Importance of Maturation for Antitumor Immunity of Dendritic Cell Vaccines
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				C. L. Slingluff Jr In Reply: J. Clin. Oncol., September 15, 2004; 22(18): 3835 - 3835. [Full Text] [PDF]