Phenotypic stability of a cytotoxic T-cell line directed against an immunodominant epitope of human carcinoembryonic antigen.
CTL lines have now been generated against defined peptides of a range of human tumor-associated antigens (TAAs). One of the potential uses of these epitope-specific CTLs is in adoptive transfer immunotherapy. This is a modality, however, that will require long-term in vitro culture of CTLs. To date, little has been reported concerning the phenotypic stability of human epitope-specific CTLs as a consequence of long-term in vitro propagation via peptide stimulation. We report here the serial phenotypic characterization of a CTL line directed against an immunodominant epitope (YLSGANLNL, designated CAP-1) of human carcinoembryonic antigen (CEA). This CTL line was derived from peripheral blood mononuclear cells of a patient with metastatic carcinoma who had been treated with a recombinant CEA-vaccinia vaccine in a Phase I trial; the CTLs were analyzed through 20 in vitro cycle passages of stimulation with CAP-1 peptide and interleukin 2 in the presence of autologous antigen-presenting cells. The CTL line was shown to be phenotypically stable in terms of high levels of cytokine (IFN-gamma, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor) production, expression of homing-adhesion molecules, ability to lyse peptide-pulsed targets, and ability to lyse human carcinoma cells endogenously expressing CEA in a MHC-restricted manner. Vbeta T-cell receptor gene usage was also analyzed. These studies thus present a rationale for the use of long-term cultured epitope-specific human CTLs, directed against a human TAA for potential adoptive transfer immunotherapy protocols.
Tsang
K Y
KY
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-1750, USA.
Zhu
M
M
Nieroda
C A
CA
Correale
P
P
Zaremba
S
S
Hamilton
J M
JM
Cole
D
D
Lam
C
C
Schlom
J
J
D015703:Antigens, CD / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis; D018968:CD58 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D003110:Colonic Neoplasms; D015179:Colorectal Neoplasms; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D039441:Integrin alpha4; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015704:CD4 Antigens; D018968:CD58 Antigens; D016827:CD8 Antigens; D002272:Carcinoembryonic Antigen; D000939:Epitopes; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4