MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer : characterization and antigen-specific activation

A potential target for development of tumor-specific immunotherapeutic strategies is the MAGE-1 gene. We have utilized a recently developed recombinant canarypox (ALVAC) virus vector containing the MAGE-1 gene (vCP235) to activate CTLs from a breast cancer patient bearing a MAGE-1+ tumor. Tumor-infi...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1996, Vol.56 (1), p.16-20
Main Authors: TOSO, J. F, COREEN OEI, FARSHID OSHIDARI, TARTAGLIA, J, PAOLETTI, E, LYERLY, H. K, SOHEL TALIB, WEINHOLD, K. J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antigen Presentation
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Antineoplastic agents
Base Sequence
Biological and medical sciences
Breast Neoplasms - immunology
Breast Neoplasms - therapy
Carcinoma - immunology
Carcinoma - therapy
Female
Gene Transfer Techniques
Humans
Immunotherapy
Immunotherapy, Adoptive
Lymphocyte Activation - immunology
Lymphocytes, Tumor-Infiltrating - immunology
Medical sciences
Melanoma-Specific Antigens
Middle Aged
Molecular Sequence Data
Neoplasm Proteins
Pharmacology. Drug treatments
T-Lymphocytes, Cytotoxic - immunology
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Summary:A potential target for development of tumor-specific immunotherapeutic strategies is the MAGE-1 gene. We have utilized a recently developed recombinant canarypox (ALVAC) virus vector containing the MAGE-1 gene (vCP235) to activate CTLs from a breast cancer patient bearing a MAGE-1+ tumor. Tumor-infiltrating lymphocytes (TILs) obtained from the tumor of a patient were stimulated in vitro with irradiated autologous peripheral blood mononuclear cells acutely infected with the vCP235 construct. These TILs preferentially expanded approximately 6-fold over a 16-day culture period and specifically recognized an allogeneic transformed B-cell line acutely infected with a vaccinia-MAGE-1 recombinant targeting vector (vP1188) in the context of HLA-A2 and/or B7. TCR V beta analysis of in vitro expanded T cells by a quantitative multiprobe RNase protection assay revealed preferential expansion of TCR V beta 6.3 and V beta 6.4. In addition, homologous T-cell receptor beta CDR3 joining sequences were found in the in vitro stimulated cultures. These results suggest that tumor antigen-specific, MHC-restricted CTLs may be derived from precursor CTLs present in TILs obtained from patients with MAGE-1+ tumors by in vitro stimulation with recombinant avipox MAGE-1 virus-infected autologous cells. Collectively, these findings provide a rationale for tumor-associated antigen-based immunization as a means of activating precursor CTLs residing in patients with tumors expressing defined tumor-associated antigens such as MAGE-1.
ISSN:0008-5472
1538-7445