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Immunization With Melan-A Peptide-Pulsed Peripheral Blood Mononuclear Cells Plus Recombinant Human Interleukin-12 Induces Clinical Activity and T-Cell Responses in Advanced Melanoma

Amy C. Peterson, Helena Harlin, Thomas F. Gajewski

From the University of Chicago, Departments of Pathology and Medicine, Section of Hematology/Oncology, and the Ben May Institute for Cancer Research, Chicago, IL.

Address reprint requests to Thomas F. Gajewski, MD, PhD, University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637; email: tgajewsk{at}medicine.bsd.uchicago.edu.

Purpose: Preclinical studies showed that immunization with peripheral blood mononuclear cells (PBMC) loaded with tumor antigen peptides plus interleukin-12 (IL-12) induced CD8⁺ T-cell responses and tumor rejection. We recently determined that recombinant human (rh) IL-12 at 30 to 100 ng/kg is effective as a vaccine adjuvant in patients. A phase II study of immunization with Melan-A peptide-pulsed PBMC + rhIL-12 was conducted in 20 patients with advanced melanoma.

Patients and Methods: Patients were HLA-A2–positive and had documented Melan-A expression. Immunization was performed every 3 weeks with clinical re-evaluation every three cycles. Immune responses were measured by ELISpot assay before and after treatment and through the first three cycles, and were correlated with clinical outcome.

Results: Most patients had received prior therapy and had visceral metastases. Nonetheless, two patients achieved a complete response, five patients achieved a minor or mixed response, and four patients had stable disease. The median survival was 12.25 months for all patients and was not yet reached for those with a normal lactate dehydrogenase. There were no grade 3 or 4 toxicities. Measurement of specific CD8⁺ T-cell responses by direct ex vivo ELISpot revealed a significant increase in interferon gamma–producing T cells against Melan-A (P = .015) after vaccination, but not against an Epstein-Barr virus control peptide (P = .86). There was a correlation between the magnitude of the increase in Melan-A–specific cells and clinical response (P = .046).

Conclusion: This immunization approach may be more straightforward than dendritic cell strategies and seems to have clinical activity that can be correlated to a biologic end point.

Supported by the Burroughs Wellcome Fund, Research Triangle Park, NC, and the Cancer Research Institute, New York, NY.

A.P. and H.H. contributed equally to this work.

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