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Open Access 01-07-2011 | Original article

Successful treatment of metastatic melanoma by adoptive transfer of blood-derived polyclonal tumor-specific CD4+ and CD8+ T cells in combination with low-dose interferon-alpha

Authors: Els M. E. Verdegaal, Marten Visser, Tamara H. Ramwadhdoebé, Caroline E. van der Minne, Jeanne A. Q. M. J. van Steijn, Ellen Kapiteijn, John B. A. G. Haanen, Sjoerd H. van der Burg, Johan W. R. Nortier, Susanne Osanto

Published in: Cancer Immunology, Immunotherapy | Issue 7/2011

Abstract

A phase I/II study was conducted to test the feasibility and safety of the adoptive transfer of tumor-reactive T cells and daily injections of interferon-alpha (IFNα) in metastatic melanoma patients with progressive disease. Autologous melanoma cell lines were established to generate tumor-specific T cells by autologous mixed lymphocyte tumor cell cultures using peripheral blood lymphocytes. Ten patients were treated with on average 259 (range 38–474) million T cells per infusion to a maximum of six infusions, and clinical response was evaluated according to the response evaluation criteria in solid tumors (RECIST). Five patients showed clinical benefit from this treatment, including one complete regression, one partial response, and three patients with stable disease. No treatment-related serious adverse events were observed, except for the appearance of necrotic-like fingertips in one patient. An IFNα-related transient leucopenia was detected in 6 patients, including all responders. One responding patient displayed vitiligo. The infused T-cell batches consisted of tumor-reactive polyclonal CD8+ and/or CD4+ T cells. Clinical reactivity correlated with the functional properties of the infused tumor-specific T cells, including their in vitro expansion rate and the secretion of mainly Th1 cytokines as opposed to Th2 cytokines. Our study shows that relatively low doses of T cells and low-dose IFNα can lead to successful treatment of metastatic melanoma and reveals a number of parameters potentially associated with this success.

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Title: Successful treatment of metastatic melanoma by adoptive transfer of blood-derived polyclonal tumor-specific CD4+ and CD8+ T cells in combination with low-dose interferon-alpha
Authors: Els M. E. Verdegaal
Marten Visser
Tamara H. Ramwadhdoebé
Caroline E. van der Minne
Jeanne A. Q. M. J. van Steijn
Ellen Kapiteijn
John B. A. G. Haanen
Sjoerd H. van der Burg
Johan W. R. Nortier
Susanne Osanto
Publication date: 01-07-2011
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 7/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1004-8

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