Journal of Molecular Medicine

, Volume 75, Issue 4, pp 290–296

Induction of tumor-specific cytotoxic T lymphocytes by immunization with autologous tumor cells and interleukin-2 gene transfected fibroblasts

  • Andreas Mackensen
  • Hendrik Veelken
  • Michael Lahn
  • Sebastian Wittnebel
  • Daniel Becker
  • Gabriele Köhler
  • Peter Kulmburg
  • Ulrich Brennscheidt
  • Felicia Rosenthal
  • Brigitte Franke
  • Roland Mertelsmann
  • A. Lindemann
ORIGINAL ARTICLE

DOI: 10.1007/s001090050114

Cite this article as:
Mackensen, A., Veelken, H., Lahn, M. et al. J Mol Med (1997) 75: 290. doi:10.1007/s001090050114

Abstract

 In a phase I trial designed to study a vaccine composed of autologous tumor cells and interleukin-2 gene transfected fibroblasts we analyzed lymphocytes infiltrating the vaccination site (VIL) in two melanoma patients. Functional studies demonstrated that numbers of MHC class I restricted cytotoxic T cells directed against the autologous tumor had increased at the immunization site in both cases. Analysis of the variability of T cell receptors (TCR) in the VIL of one patient revealed that the cytotoxic T lymphocytes consisted of a predominant population of TCRBV21S3+ T cells. Enrichment of this subpopulation to more than 99% by specific anti-TCRBV21S3 monoclonal antibody linked immunomagnetic beads and sequencing of the TCR-β chain disclosed exactly the same V-D-J junctional sequence in all eight TCRBV21 transcripts from these VIL. The identical sequence was also detected in all eight TCRBV21 transcripts from the patient’s tumor-infiltrating lymphocytes, indicating that the same CTL clone had infiltrated the tumor, circulated in the peripheral blood, and was amplified at the vaccination site. The TCRBV21S3+ T cells were also found to display an MHC class I restricted cytotoxic activity specifically directed against the autologous tumor cells. At the beginning of treatment these cells were undetectable at the vaccination site and delayed-type hypersensitivity testing was negative, contrasting with the positive results after therapy. Thus it is likely that vaccination with autologous tumor cells plus interleukin-2 gene transfected allogeneic fibroblasts had induced not only local accumulation but also an increase in the frequency of circulating tumor specific CTL.

Key words Gene TherapyVaccinationMelanomaCytotoxic T lymphocytesTumor-infiltrating lymphocytes

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Andreas Mackensen
    • 1
  • Hendrik Veelken
    • 1
  • Michael Lahn
    • 1
  • Sebastian Wittnebel
    • 1
  • Daniel Becker
    • 1
  • Gabriele Köhler
    • 2
  • Peter Kulmburg
    • 1
  • Ulrich Brennscheidt
    • 1
  • Felicia Rosenthal
    • 1
  • Brigitte Franke
    • 1
  • Roland Mertelsmann
    • 1
  • A. Lindemann
    • 1
  1. 1.Department of Hematology/Oncology, University of Freiburg Medical Center, Hugstetterstrasse 55, D-79106 Freiburg, GermanyDE
  2. 2.Department of Pathology, University of Freiburg Medical Center, Hugstetterstrasse 55, D-79106 Freiburg, GermanyDE