Identification+of+human+tumor+antigens+by+serological+expression+cloning+c+an+online+review+on+SEREX

Identification of human tumor antigens by serological expression cloning – an online review on SEREX 2004 Cancer Immunology Cornell http://cancerimmunity.org/serex/

4 phases of research to find antibodies that distinguish cancer from normal

1 inject rabbits with human cancer 2 cytotoxic alloantibodies prepared in inbred mice against cell surface "differentiation antigens" 3 autologous typing; cultured tumor cells

SEREX approach first developed by q This limitation in autologous typing has been overcome by a new approach introduced by Michael Pfreundschuh and his colleagues Ugur Sahin and Ozlem Türeci at the University of Saarland (19, 20). SEREX, for serological analysis of recombinant cDNA expression libraries

SEREX provides a way to analyze the humoral response to intracellular cancer antigens

nice SEREX methodology figure

problems eliminating sera against bacteria or phage presence of B cells in tumors autoantibodies against antigens having nothing to do with cancer

characterization of SEREX clones

q The fact that a number of these genes are widely expressed in normal tissues indicates that cancer-specific recognition can occur in the absence of cancer-specific expression. The basis for this cancer-specific immunogenicity is one of the central challenges that needs resolving

usually tumor and serum from the same patient are used, but other variations have been explored

note about Cancer Immunome Database q A SEREX collaborative group was established in 1996 by the Ludwig Institute for Cancer Research, involving investigators at the University of Saarland (Homburg, Germany), Ludwig Institute Branches in New York, Melbourne, and London (University College), Aichi Cancer Center (Japan), Krankenhaus Nordwest (Frankfurt, Germany), and Moscow State University (Russia). A database (150) incorporating SEREX data has been organized by Victor Jongeneel (Director of Information Technology, Ludwig Institute for Cancer Research), and 2593 sequences derived from 2169 clones have been deposited at last count (February 2004).

many SEREX antigens for many different types of cancers have been identified melanoma,

some of the colon cancer antigens have frameshift mutations and frameshift mutations associated with microsatellites AD034 (this gene had a frameshift mutation) (12384809) (found from Identification of human tumor antigens by serological expression cloning – an online review on SEREX) CDX2 (frameshift mutation due to microsatellite) found by Ishikawa (14500396) (found by "Identification of human tumor antigens by serological expression cloning c an online review on SEREX" paper)

quite a few transcription factors identified

q Low-yield SEREX screening is, in fact, not uncommonly encountered, most likely reflecting low tumor immunogenicity or low host immune reactivity, or both.

//what's the difference between Hodgkin and non-Hodgkin lymphoma?// //Hodgkin's has large Reed-Steinberg cells or something//

//Classification of sEREX-defined antigens section//

//q// //it is particularly striking that so many of the SEREX-defined antigens are nuclear proteins (e.g., enzymes and factors involved in DNA replication, transcriptional control, RNA elongation, DNA repair, including zinc finger proteins, RNA helicases, proteins related to the mitotic apparatus, and chromosome condensation proteins)//

//cancer/testis antigens// //MAGE, BAGE, and GAGE some of the main antigens// //mutational antigens// //hot spots of genetic aberrations in chromosomes// //differentiation antigens//

what is a CT antigen? q A CT antigen is a cancer-testis antigen The cancer-testis (CT) antigens are expressed by tumors of different histological types at varying frequencies (10-40%).(83 They are typically not expressed by normal tissues, with the exception of testis in males and the placenta in pregnant females. The CT antigen expressing cells in testis are the male germ cells (ie, spermatogonia).

amplified or overexpressed antigens gene amplification splice variant antigens

q Human endogenous retrovirus (HERV)-related sequences have been shown to represent at least 1% of the human genome

^wow so much

Serological screening showed antibodies against the HERV-K gag protein in a significant number of prostate cancer patients, suggesting that retroviral antigens may potentially be cancer vaccine targets.

Past studies have demonstrated a high frequency of autoantibodies to known normal tissue autoantigens in cancer patients (80), and it would not be surprising that a significant proportion of the currently defined SEREX antigens are autoantigens of this kind.

mutations have been detected so rarely in SEREX-defined genes (29)

q Reactivity is not restricted to patients with the corresponding cancer type; sera from patients with other forms of cancer (e.g., lung or breast cancers) recognize a proportion of the antigens derived from colon and renal cancer.

//what is the definition of petit serology?//

what is the definition of grand serology?

^ seems to basically only be referenced in this paper

q because production of IgG antibodies is known to require CD4 T-cell help, SEREX analysis can be viewed as a way to define the CD4 T-cell repertoire against human tumor antigens.

q Because the definition of targets for T-cell recognition is a far more complex and laborious task than defining antibody targets, current technologies place a limit on the number of antigens that can be analyzed from the T-cell perspective.

q identifying the complete repertoire of immunogenic gene products in human cancer – what is becoming known as the cancer immunome – is now an achievable goal for tumor immunology.

q Since the establishment of the SEREX database in 1997, later incorporated into the Cancer Immunome Database (150), 2593 sequences derived from 2169 clones have been deposited (February 2004), most of them contributed by the LICR SEREX Collaborative Group.

q On the other hand, even in a very recent study of lung cancer (144), only about one third of the isolated genes were already in the database, suggesting that the pool of immunogenic cancer antigens, although apparently finite in size, is still far from completely defined.

q Uemura //et al//. (107) analyzed two hepatocellular carcinoma patients in Japan, and several tumor-associated genes were isolated, including SART1, ROCK-1, gamma catenin, heat-shock protein, etc. 107 = Identification of the antigens predominantly reacted with serum from patients with hepatocellular carcinoma. PMID 12733146