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

J Mol Med (Berl). 1997 Apr;75(4):290-6. doi: 10.1007/s001090050114.


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-beta 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line
  • Cytotoxicity, Immunologic
  • Female
  • Fibroblasts / transplantation
  • Humans
  • Immunotherapy, Adoptive / methods
  • Interleukin-2 / genetics*
  • Lymphocytes, Tumor-Infiltrating
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Transplantation
  • Receptors, Antigen, T-Cell, alpha-beta / blood
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Skin / immunology
  • T-Lymphocytes
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccination


  • Cancer Vaccines
  • Interleukin-2
  • Receptors, Antigen, T-Cell, alpha-beta