Phenotypic stability of a cytotoxic T-cell line directed against an immunodominant epitope of human carcinoembryonic antigen

• Published in: Clinical cancer research 1997-12, Vol.3 (12), p.2439-2449
• Main Authors: TSANG, K. Y, ZHU, M, NIERODA, C. A, CORREALE, P, ZAREMBA, S, HAMILTON, J. M, COLE, D, LAM, C, SCHLOM, J
• Format: Article
• Language: English
• Subjects: Antigens, CD - analysis; Biological and medical sciences; Carcinoembryonic Antigen - biosynthesis; Carcinoembryonic Antigen - genetics; Carcinoembryonic Antigen - immunology; CD4 Antigens - analysis; CD58 Antigens - analysis; CD8 Antigens - analysis; Cell Line; Colonic Neoplasms; Colorectal Neoplasms; Cytotoxicity, Immunologic; Epitopes - immunology; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunophenotyping - methods; Integrin alpha4; Intercellular Adhesion Molecule-1 - analysis; Medical sciences; Polymerase Chain Reaction; Recombinant Proteins - biosynthesis; Recombinant Proteins - immunology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; T-Lymphocytes, Cytotoxic - immunology; Transfection; Tumor Cells, Cultured; Tumors
• ISSN: 1078-0432; 1557-3265

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.