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Immunization Using Autologous Dendritic Cells Pulsed with the Melanoma-Associated Antigen gp100-Derived G280-9V Peptide Elicits CD8⁺ Immunity

Authors' Affiliations: ¹ Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital; ² Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; ³ Division of Oncology, Washington University School of Medicine, St. Louis, Missouri; and ⁴ University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Frank G. Haluska, Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital, GRJ 1021, 55 Fruit Street, Boston, MA 02114. Phone: 617-724-7081; Fax: 617-726-6974; E-mail: haluska.frank{at}mgh.harvard.edu.

Purpose: To determine the toxicity, maximal tolerated dose, and clinical and immunologic response to autologous dendritic cells pulsed with melanoma-associated antigen gp100-derived G280-9V peptide.

Patients and Methods: Twelve HLA-A*0201⁺ patients with advanced melanoma were administered dendritic cells pulsed with G280-9V peptide. Cohorts of three patients were administered 5 x 10⁶, 15 x 10⁶, and 50 x 10⁶ cells i.v. every 3 weeks for six doses according to a dose escalation scheme. Three additional patients were treated at the highest dose. No additional cytokines or therapies were coadministered. The immunogenicity of G280-9V-pulsed dendritic cells was measured by IFN- ELISPOT assay, tetramer assay, and ⁵¹Cr release assay comparing prevaccination to postvaccination blood samples. Response to treatment was assessed by Response Evaluation Criteria in Solid Tumors.

Results: CD8⁺ immunity to the native G280 was observed in 8 (67%) patients as measured by ELISPOT and in 12 (100%) patients as measured by tetramer assay. Of the 9 patients tested, 9 (100%) had measurable high-avidity CTL activity as defined by lysis of allogeneic melanoma lines, which coexpress HLA-A*0201 and gp100. The median follow-up of the entire cohort is 43.8 months. Two (17%) partial responses were observed and 3 (25%) patients had stable disease. The median survival of the treated population was 37.6 months. At this time, three patients are alive, including one patient who continues to respond without additional treatment.

Conclusion: The high rate of immunization as measured by three independent assays and the occurrence of clinical regression support continued investigation of G280-9V peptide as a candidate epitope in melanoma vaccine formulations.

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