Comparative assessment of TCRBV diversity in T lymphocytes present in blood, metastatic lesions, and DTH sites of two melanoma patients vaccinated with an IL-7 gene-modified autologous tumor cell vaccine

Marilisa Carsana, Gabrina Tragni, Gabriella Nicolini, Ilaria Bersani, Giorgio Parmiani, Andrea Anichini, Yuan Sheng Sun, Peter Möller, Dirk Schadendorf, Maria Luisa Sensi

Research output: Contribution to journalArticle

Abstract

A phase I clinical trial using autologous, IL-7 gene-modified tumor cells in patients with disseminated melanoma has been recently completed. Although no major clinical responses were observed, increased antitumor cytotoxicity was measured in postvaccine peripheral blood lymphocytes in a subset of treated patients. To analyze the in situ immune response, the T cell receptor β-chain variable region (BV) repertoire of T cells infiltrating postvaccine lesions was studied in two patients, and compared with that of T cells present in prevaccine ones, in peripheral blood lymphocytes, and, in one patient, in delayed type hypersensitivity (DTH) sites of autologous melanoma inoculum. A relative expansion of T cells expressing few BVs was observed in all postvaccine metastases, and their intratumoral presence was confirmed by immunohistochemistry. Length pattern analysis of the complementarity determining region 3 (CDR3) indicated that the repertoire of T cells expressing some of these BVs was heterogeneous. At difference, CDR3, β-chain joining region usage, and sequence analysis enabled us to demonstrate, within a T-cell subpopulation commonly expanded at DTH sites and at the postvaccine lesion of patient 1, that both DTH sites contained identical dominant T-cell clonotypes. One of them was also expressed at increased relative frequency in the postvaccine lesion compared to prevaccine specimens. These results provide evidence for immunological changes, including in situ clonally expanded T cells, in metastases of patients vaccinated with IL-7 gene-transduced cells.

Original languageEnglish
Pages (from-to)243-253
Number of pages11
JournalCancer Gene Therapy
Volume9
Issue number3
DOIs
Publication statusPublished - 2002

Keywords

  • Gene transfer
  • IL-7
  • Melanoma
  • T lymphocytes
  • T-cell receptor
  • Tumor vaccination

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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