Originally published as JCO Early Release 10.1200/JCO.2008.17.3161 on September 22 2008

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Helper T-Cell Responses and Clinical Activity of a Melanoma Vaccine With Multiple Peptides From MAGE and Melanocytic Differentiation Antigens

Craig L. Slingluff, Jr, Gina R. Petroni, Walter Olson, Andrea Czarkowski, William W. Grosh, Mark Smolkin, Kimberly A. Chianese-Bullock, Patrice Y. Neese, Donna H. Deacon, Carmel Nail, Priscilla Merrill, Robyn Fink, James W. Patterson, Patrice K. Rehm

From the Department of Surgery/Division of Surgical Oncology, Department of Public Health Sciences, Cancer Center, Department of Medicine/Division of Hematology-Oncology, Department of Pathology, and Department of Radiology, University of Virginia Health System, Charlottesville, VA

Corresponding author: Craig L. Slingluff Jr, MD, 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 A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel melanoma vaccine comprising six melanoma-associated peptides defined as antigenic targets for melanoma-reactive helper T cells. Source proteins for these peptides include MAGE proteins, MART-1/MelanA, gp100, and tyrosinase.

Patients and Methods Thirty-nine patients with stage IIIB to IV melanoma were vaccinated with this six-peptide mixture weekly at three dose levels, with a preceding phase I dose escalation and subsequent random assignment among the dose levels. Helper T-lymphocyte responses were assessed by in vitro proliferation assay and delayed-type hypersensitivity skin testing. Patients with measurable disease were evaluated for objective clinical response by Response Evaluation Criteria in Solid Tumors.

Results Vaccination with the helper peptide vaccine was well tolerated. Proliferation assays revealed induction of T-cell responses to the melanoma helper peptides in 81% of patients. Among 17 patients with measurable disease, objective clinical responses were observed in two patients (12%), with response durations of 1 and 3.9+ years. Durable stable disease was observed in two additional patients for periods of 1.8 and 4.6+ years.

Conclusion Results of this study support the safety and immunogenicity of a vaccine comprised of six melanoma helper peptides. There is also early evidence of clinical activity.

published online ahead of print at www.jco.org on September 22, 2008

Supported by National Institutes of Health (NIH)/National Cancer Institute (NCI) Grant No. R21 CA105777 (C.L.S). Support was also provided by a University of Virginia (UVA) Cancer Center Support grant (Grant No. NIH/NCI P30 CA44579, Clinical Trials Office, Tissue Procurement Facility, Flow Cytometry Core, and Biomolecular Core Facility) and the UVA General Clinical Research Center (Grant No. NIH M01 RR00847). Peptides used in this vaccine were prepared with philanthropic support from Alice T. and William H. Goodwin Jr. Granulocyte-macrophage colony-stimulating factor (Berlex, now Bayer) and Montanide ISA-51 (Seppic Inc) were used in the vaccines in this trial, but these were paid for by UVA.

Presented in part at the 21st Annual Meeting of the International Society for the Biological Therapy of Cancer, October 26-29, 2006, Los Angeles, CA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00089219 [ClinicalTrials.gov]

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