Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 158K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Romero, P. Articles by Cerundolo, V. Search for Related Content PubMed PubMed Citation Articles by Romero, P. Articles by Cerundolo, V. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Melanoma Social Bookmarking                            What's this?

Articles

Pedro Romero^*, P. Rod Dunbar, Danila Valmori^*, Mikaël Pittet^*, Graham S. Ogg, Donata Rimoldi^*, Ji-Li Chen, Danielle Liénard^*,, Jean-Charles Cerottini^*, and Vincenzo Cerundolo

From the ^* Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch, and the Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; and the Institute of Molecular Medicine, Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom

Characterization of cytolytic T lymphocyte (CTL) responses to tumor antigens has been impeded by a lack of direct assays of CTL activity. We have synthesized reagents ("tetramers") that specifically stain CTLs recognizing melanoma antigens. Tetramer staining of tumor-infiltrated lymph nodes ex vivo revealed high frequencies of tumor-specific CTLs which were antigen-experienced by surface phenotype. In vitro culture of lymph node cells with cytokines resulted in very large expansions of tumor-specific CTLs that were dependent on the presence of tumor cells in the lymph nodes. Tetramer-guided sorting by flow cytometer allowed isolation of melanoma-specific CTLs and confirmation of their specificity and their ability to lyse autologous tumor cells. Our results demonstrate the value of these novel reagents for monitoring tumor-specific CTL responses and for generating CTLs for adoptive immunotherapy. These data also indicate that strong CTL responses to melanoma often occur in vivo, and that the reactive CTLs have substantial proliferative and tumoricidal potential.

Key Words: melanoma • Melan-A/MART-1 • tyrosinase • immunotherapy • tumor immunity

This work is partly funded by the United Kingdom Medical Research Council and Cancer Research Campaign. P.R. Dunbar is the Girdlers Research Fellow at Green College.

P. Romero and P.R. Dunbar contributed equally to this work.

Abbreviations used: β2M, β2-microglobulin; LDA, limiting dilution assay; NLN, non–tumor-infiltrated lymph node; rh, recombinant human; RT, reverse transcription; TILN, tumor-infiltrated lymph node.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS