Intralesional selection of T cell clonotypes in the immune response to melanoma antigens occurring during vaccination

Marialuisa Sensi, Cinthia Farina, Cristina Maccalli, Andrea Anichini, David Berd, Giorgio Parmiani

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

T cells infiltrating pre- and postvaccine metastases obtained from melanoma patients vaccinated with either dinitrophenyl (DNP)-modified autologous tumor or with the MAGE-3.A1 peptide display selective T cell receptor (TCR) β chain variable region (BV) repertoire changes at the tumor site as a consequence of vaccination. Restricted sets of BV families expand in all postvaccine lesions when compared with prevaccine specimens and often contain dominant clones. A protocol devised to obtain T cell lines highly enriched for expression of a given BV region through the use of anti-BV monoclonal antibodies was used to understand whether responses to specific antigen(s) accounted for these clonal expansions. In one of the patients vaccinated with DNP-modified tumor cells, BV-driven selection of the T lymphocytes expanded in two infiltrated postvaccine metastases resulted in T cell lines able to exert HLA class I-restricted lysis of the autologous tumor. These results indicate that TCR repertoire analysis at the tumor site facilitates the detection of T cell responses elicited by a vaccine and potentially cytotoxic for the autologous tumor.

Original languageEnglish
Pages (from-to)198-204
Number of pages7
JournalJournal of Immunotherapy
Volume21
Issue number3
Publication statusPublished - 1998
Externally publishedYes

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Keywords

  • Cytotoxic T lymphocytes
  • Human
  • Melanoma antigens
  • T cell receptor
  • Vaccination

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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