Targeting p53 as a General Tumor Antigen

A major barrier to the design of immunotherapeutics and vaccines for cancer is the idiosyneratic nature of many tumor antigens and the possibility that T cells may be tolerant of broadly distributed antigens. We have devised an experimental strategy that exploits species differences in protein seque...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-12, Vol.92 (26), p.11993-11997
Main Authors: Theobald, M, Biggs, J, Dittmer, D, Levine, A J, Sherman, L A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antigens, Neoplasm - immunology
Cell lines
Drug Design
Epitopes
Epitopes - chemistry
Epitopes - immunology
HIV 1
HLA-A2 Antigen - biosynthesis
HLA-A2 Antigen - genetics
HLA-A2 Antigen - immunology
Humans
Immunity (Disease)
Immunotherapy
Medical research
Mice
Mice, Inbred C57BL
Mice, Transgenic
Molecular Sequence Data
Molecules
Neoplasms - immunology
Neoplasms - therapy
Oligopeptides - chemical synthesis
Oligopeptides - chemistry
Oligopeptides - immunology
Proteins
Spleen cells
T lymphocytes
T-Lymphocytes - immunology
Tumor cell line
Tumor Suppressor Protein p53 - chemistry
Tumor Suppressor Protein p53 - immunology
Tumors
Vaccines, Synthetic
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Summary:A major barrier to the design of immunotherapeutics and vaccines for cancer is the idiosyneratic nature of many tumor antigens and the possibility that T cells may be tolerant of broadly distributed antigens. We have devised an experimental strategy that exploits species differences in protein sequences to circumvent tolerance of high-affinity T cells. HLA transgenic mice were used to obtain cytotoxic T lymphocytes specific for peptides from the human p53 tumor-suppressor molecule presented in association with HLA-A2.1. Although such p53-specific cytotoxic T cells did not recognize nontransformed human cells, they were able to lyse a wide variety of human tumor cell lines, thus confirming the existence of broadly distributed determinants that may serve as targets for immunotherapy.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.26.11993