Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine

J Natl Cancer Inst. 1995 Jul 5;87(13):982-90. doi: 10.1093/jnci/87.13.982.


Background: The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates.

Purpose: Our objective was to determine if rVCEA could elicit CEA-specific T-cell responses in humans with appropriate human leukocyte antigen (HLA) motifs.

Methods: Peripheral blood lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before and after vaccination with rV-CEA, were analyzed for T-cell response to specific 9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs.

Results: While little or no T-cell growth was seen from preimmunization PBLs of patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were obtained from PBLs of patients after vaccination with one to three cycles of stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established with a 9-amino acid peptide (CAP-1), and the CD8+/CD4+ double-positive T-cell line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced with the CEA gene using a retroviral vector, they were lysed by the V24T cell line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma cell lines were not. To further confirm the class I HLA-A2 restricted nature of the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell line was infected with a recombinant vaccinia virus expressing the HLA class I-A2 gene, and it became susceptible to V24T lysis. Cells infected with vector alone were not lysed.

Conclusions: This study demonstrates for the first time (a) the ability to generate a human cytolytic T-cell response to specific epitopes of CEA, (b) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and (c) the ability of human tumor cells to endogenously process CEA to present a specific CEA peptide in the context of major histocompatibility complex for T-cell-mediated lysis.

Implications: These findings have implications in the development of specific second-generation cancer immunotherapy protocols.

MeSH terms

  • Amino Acid Sequence
  • Carcinoembryonic Antigen / immunology*
  • Carcinoma / immunology
  • Colorectal Neoplasms / immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunodominant Epitopes / immunology*
  • Molecular Sequence Data
  • T-Lymphocytes / immunology*
  • Vaccines, Synthetic / immunology
  • Vaccinia virus / immunology*
  • Viral Vaccines / immunology*


  • Carcinoembryonic Antigen
  • Histocompatibility Antigens Class I
  • Immunodominant Epitopes
  • Vaccines, Synthetic
  • Viral Vaccines