Human neoplasms elicit multiple specific immune responses in the autologous host.

Abstract

Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with hightiter IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

Analysis of the antibody repertoire of astrocytoma patients against antigens expressed by gliomas

“…To detect more of such antigens in astrocytomas, we analyzed the B-cell repertoire of 18 patients with astrocytomas and glioblastomas against antigens expressed by autologous and allogeneic astrocytomas and other gliomas using SEREX, the serologic analysis of antigens using recombinant cDNA expression cloning. 5 Our results show that even though astrocytomas express a wide range of antigens, antibody responses against these antigens are rare in glioma patients.…”

Transductional targeting of adenovirus vectors for gene therapy

“…Another method to identify new tumor targets is 'serological identification of antigens by recombinant expression cloning' (SEREX), which was first described by Sahin et al 144 in 1995 and is based on the presence of TAA recognizing antibodies in the serum of cancer patients. In this approach, a cDNA library is constructed from tumor specimens and cloned into expression vectors.…”

“…Clones are then screened for reactivity with the serum of the autologous patient, and the nucleotide sequence of the cDNA insert is determined. 144 In previous years, several antigens that can be classified into different groups have been identified, including cancer-testis antigens, differentiation antigens, overexpressed gene products, mutated gene products, splice variants and cancer-related autoantigens. Examples of antigens discovered using this technology are melanoma antigen gene-1 (MAGE-1) in melanoma and metastasis-associated protein-1 (MTA1) in prostate cancer.…”

Antibody response to a non‐conserved C‐terminal part of human histone deacetylase 3 in colon cancer patients

“…Serological screening of tumor-derived cDNA expression library (SEREX) was carried out essentially as described earlier 1,15 with minor modifications. Briefly, a cDNA library was plated with E. coli XL-1 Blue MRF, host cells, transferred to the nitrocellulose membranes, incubated with autologous patient's serum (diluted 1/200) and alkaline phosphatase-conjugated goat anti-human Fcg secondary antibodies (Jackson ImmunoResearch, West Grove, PA) diluted 1/3,000.…”

“…Immunoscreening of tumor-derived cDNA expression libraries (SEREX) proved to be an efficient technique to clone serologically defined antigens. 1,2 Histone deacetylases (HDAC) represent the family of enzymes involved in dynamic regulation of chromatin structure during transcription, but can also deacetylate a number of non-histone substrates. [3][4][5][6][7][8][9] A growing body of evidence implicates HDAC as playing an important role in carcinogenesis, particularly, in colorectal cancer, as suggested by expression profiling of colon cancer cells treated by HDAC inhibitor trichostatin A.…”