Evaluation of Prime/Boost Regimens Using Recombinant Poxvirus/Tyrosinase Vaccines for the Treatment of Patients with Metastatic Melanoma
| Autor: | Nicholas P. Restifo, Suzanne L. Topalian, Leah R. Haworth, Linda Rogers-Freezer, Richard M. Sherry, Sharon Mavroukakis, Dennis Panicali, Andrea Abati, Steven A. Rosenberg, Kimberly R. Lindsey, Lisa C. Goldfeder, Kimberly A. Zinnack, Donald E. White, Linda Gritz, Monica Gonzales, Patricia Fetsch, Seth M. Steinberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Interleukin 2
Fowlpox Cancer Research Tyrosinase T-Lymphocytes Genetic Vectors Tyrosinase Peptide DNA Recombinant Immunization Secondary Cancer Vaccines Article chemistry.chemical_compound Interferon-gamma Medicine Humans RNA Messenger Neoplasm Metastasis Melanoma Immunization Schedule business.industry Monophenol Monooxygenase Reverse Transcriptase Polymerase Chain Reaction Poxviridae Vaccination medicine.disease Combined Modality Therapy Clinical trial Treatment Outcome Oncology chemistry Immunoglobulin G Immunology Interleukin-2 Vaccinia business medicine.drug |
| Popis: | Purpose: Two clinical trials were conducted to evaluate the clinical efficacy and immunologic impact of vaccination against the tyrosinase protein plus systemic interleukin 2 (IL-2) administration in patients with advanced metastatic melanoma.Experimental Design: Full-length tyrosinase was employed as an immunogen to induce diverse immunologic responses against a commonly expressed melanoma antigen. Heterologous prime/boost vaccination with recombinant vaccinia and fowlpox vectors encoding tyrosinase was first explored in a randomized three-arm phase II trial, in which vaccines were administered alone or concurrently with low-dose or high-dose IL-2. In a subsequent single cohort phase II trial, all patients received the same vaccines and high-dose IL-2 sequentially rather than concurrently.Results: Among a total of 64 patients treated on these trials, 8 objective partial responses (12.5%) were observed, all in patients receiving high-dose IL-2. Additional patients showed evidence of lesional regression (mixed tumor response) or overall regression that did not achieve partial response status (minor response). In vitro evidence of enhanced immunity against tyrosinase following protocol treatments was documented in 3 of 49 (6%) patients tested serologically, 3 of 23 (13%) patients tested for T-cell recognition of individual tyrosinase peptides, and 4 of 16 (25%) patients tested for T-cell recognition of full-length tyrosinase protein with real-time reverse transcription-PCR techniques.Conclusions: Whereas prime/boost immunization with recombinant vaccinia and fowlpox viruses enhanced antityrosinase immunity in some patients with metastatic melanoma, it was ineffective alone in mediating clinical benefit, and in combination with IL-2 did not mediate clinical benefit significantly different from that expected from treatment with IL-2 alone. |
| Databáze: | OpenAIRE |
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