PMID- 7629885
OWN - NLM
STAT- MEDLINE
DCOM- 19950907
LR  - 20201222
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 87
IP  - 13
DP  - 1995 Jul 5
TI  - Generation of human cytotoxic T cells specific for human carcinoembryonic antigen 
      epitopes from patients immunized with recombinant vaccinia-CEA vaccine.
PG  - 982-90
AB  - 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.
FAU - Tsang, K Y
AU  - Tsang KY
AD  - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National 
      Institutes of Health, Bethesda, MD 20892, USA.
FAU - Zaremba, S
AU  - Zaremba S
FAU - Nieroda, C A
AU  - Nieroda CA
FAU - Zhu, M Z
AU  - Zhu MZ
FAU - Hamilton, J M
AU  - Hamilton JM
FAU - Schlom, J
AU  - Schlom J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Vaccines, Synthetic)
RN  - 0 (Viral Vaccines)
SB  - IM
CIN - J Natl Cancer Inst. 1995 Jul 5;87(13):949-51. PMID: 7629879
MH  - Amino Acid Sequence
MH  - Carcinoembryonic Antigen/*immunology
MH  - Carcinoma/immunology
MH  - Colorectal Neoplasms/immunology
MH  - Flow Cytometry
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Immunodominant Epitopes/*immunology
MH  - Molecular Sequence Data
MH  - T-Lymphocytes/*immunology
MH  - Vaccines, Synthetic/immunology
MH  - Vaccinia virus/*immunology
MH  - Viral Vaccines/*immunology
EDAT- 1995/07/05 00:00
MHDA- 1995/07/05 00:01
CRDT- 1995/07/05 00:00
PHST- 1995/07/05 00:00 [pubmed]
PHST- 1995/07/05 00:01 [medline]
PHST- 1995/07/05 00:00 [entrez]
AID - 10.1093/jnci/87.13.982 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 1995 Jul 5;87(13):982-90. doi: 10.1093/jnci/87.13.982.