1.
The specific immune response to tumor antigen CP1 and its correlation with improved survival in colon cancer patients.
Liu, FF, Dong, XY, Pang, XW, Xing, Q, Wang, HC, Zhang, HG, Li, Y, Yin, YH, Fant, M, Ye, YJ, et al
Gastroenterology. 2008;(4):998-1006
Abstract
BACKGROUND & AIMS The present study was undertaken to determine the expression of a newly identified tumor antigen cancer-placenta 1 (CP1) in colorectal carcinoma (CRC) and explore the CP1-specific immune response in CRC patients and its correlation with patient survival. METHODS CP1 expression was determined by reverse-transcription polymerase chain reaction, immunohistochemistry, and Western blot analysis. Serum antibodies against CP1 were detected by enzyme-linked immunosorbent assay, and T-cell response was measured by interferon-gamma/granzyme-B release enzyme-linked immunospot assays. The HLA-A2-restricted epitopes in CP1 were predicted by bioinformatics and then experimentally validated by enzyme-linked immunospot assay. RESULTS CP1 expression was detected in a significant number of CRC tissues, reaching 47.6% at the messenger RNA (mRNA) level and 28.6% at the protein level. Of patients with CP1 mRNA(+) tumors, more than 50% had CP1-responsive CD4(+) and CD8(+) T cells and 30% spontaneous-occurring antibodies against CP1. Further studies revealed 2 dominant HLA-A2-restricted epitopes in the CP1 antigen: p31-39 and p58-66. In a follow-up study up to 33 months after surgery, 9 of the 10 patients with CP1-specific CD8 T-cell response survived, whereas 6 of the 8 nonresponders died. Kaplan-Meier analysis indicated a significant correlation between T-cell response and patient survival. CONCLUSIONS CP1 represents a new class of tumor-specific shared antigen. Its high expression in CRC tissues, prevalence of CP1-specific immune responses in CP1 mRNA(+) CRC patients, and positive correlation with survival suggest that the antigen may be a useful target for cancer immunotherapy.
2.
Tumor-specific shared antigenic peptides recognized by human T cells.
Van Der Bruggen, P, Zhang, Y, Chaux, P, Stroobant, V, Panichelli, C, Schultz, ES, Chapiro, J, Van Den Eynde, BJ, Brasseur, F, Boon, T
Immunological reviews. 2002;:51-64
Abstract
The first tumor-specific shared antigens and the cancer-germline genes that code for these antigens were identified with antitumor cytolytic T lymphocytes obtained from cancer patients. A few HLA class I-restricted antigenic peptides were identified by this 'direct approach'. A large set of additional cancer-germline genes have now been identified by purely genetic approaches or by screening tumor cDNA expression libraries with the serum of cancer patients. As a result, a vast number of sequences are known that can code for tumor-specific shared antigens, but most of the encoded antigenic peptides have not yet been identified. We review here recent 'reverse immunology' approaches for the identification of new antigenic peptides. They are based on in vitro stimulation of naive T cells with dendritic cells that have either been loaded with a cancer-germline protein or that have been transduced with viruses carrying cancer-germline coding sequences. These approaches have led to the identification of many new antigenic peptides presented by class I or class II molecules. We also describe some aspects of the processing and presentation of these antigenic peptides.