3 research outputs found
Growth inhibition of human colorectal carcinomas by a monoclonal antibody directed against the IGF-I-receptor
Identification of tumor-associated antigens by large-scale analysis of genes expressed in human colorectal cancer
Despite the high prevalence of colon cancer in the
world and the great interest in targeted anti-cancer therapy, only
few tumor-specific gene products have been identified that could
serve as targets for the immunological treatment of colorectal cancers.
The aim of our study was therefore to identify frequently expressed
colon cancer-specific antigens. We performed a large-scale analysis
of genes expressed in normal colon and colon cancer tissues isolated
from colorectal cancer patients using massively parallel signal
sequencing (MPSS). Candidates were additionally subjected to experimental
evaluation by semi-quantitative RT-PCR on a cohort of colorectal
cancer patients. From a pool of more than 6000 genes identified unambiguously
in the analysis, we found 2124 genes that were selectively expressed
in colon cancer tissue and 147 genes that were differentially expressed
to a significant degree between normal and cancer cells. Differential
expression of many genes was confirmed by RT-PCR on a cohort of
patients. Despite the fact that deregulated genes were involved
in many different cellular pathways, we found that genes expressed
in the extracellular space were significantly over-represented in
colorectal cancer. Strikingly, we identified a transcript from a
chromosome X-linked member of the human endogenous retrovirus (HERV)
H family that was frequently and selectively expressed in colon
cancer but not in normal tissues. Our data suggest that this sequence
should be considered as a target of immunological interventions
against colorectal cancer
Molecular and immunological evaluation of the expression of cancer/testis gene products in human colorectal cancer.
Tumor-specific gene products, such as cancer/testis (CT) antigens, constitute promising targets for the development of T cell vaccines. Whereas CT antigens are frequently expressed in melanoma, their expression in colorectal cancers (CRC) remains poorly characterized. Here, we have studied the expression of the CT antigens MAGE-A3, MAGE-A4, MAGE-A10, NY-ESO-1 and SSX2 in CRC because of the presence of well-described HLA-A2-restricted epitopes in their sequences. Our analyses of 41 primary CRC and 14 metastatic liver lesions confirmed the low frequency of expression of these CT antigens. No increased expression frequencies were observed in metastatic tumors compared to primary tumors. Histological analyses of CRC samples revealed heterogeneous expression of individual CT antigens. Finally, evidence of a naturally acquired CT antigen-specific CD8(+) T cell response could be demonstrated. These results show that the expression of CT antigens in a subset of CRC patients induces readily detectable T cell responses