| Project Leader:
|
Sergei A.Nedospasov, Ph.D., D.Sci.
Head, Laboratory of Molecular Immunology, A.N. Belozersky Institute of Physico-Chemical Biology. |
| Address:
|
A.N.Belozersky Institute of Physico-Chemical Biology,
Center for Molecular Medicine Moscow State University, 119899, Moscow, Russia. |
| Tel/fax: | +7 (095) 939-1445 |
| E-mail: | snedos@online.ru |
Brief project description:
This project is carried out in close collaboration
with Ludwig Institute for Cancer Research in New York (Dr. Lloyd Old, Director,
Dr. Matthew Scanlan, Assistant Member), Oncological Research Center (Prof.
Michail Litchinitser, Dr. Andrei Mestcheryakov) and Engelhardt Institute
of Molecular Biology (Dr. Dmitry Kuprash, Dr. Regina Turetskaya) in Moscow,
Medizinische Klinik, Haematologie-Onkologie, Frankfurt, Germany (Dr. Elke
Jager, Prof. Alexander Knuth), and Dr. Yuichi Obata from Aichi Cancer Center
Research Institute, Nagoya, Japan.
Tumor antigens, proteins that are expressed by malignant
but not by normal cells, have been the targets of extensive studies for
decades. For example, the immunodetection of one such antigen, alpha-fetoprotein,
which is selectively expressed on liver cancer cells, has been included
in routine diagnostic test. The search for new tumor antigens has been
much simplified with development of SEREX (serological analysis of recombinant
cDNA expression libraries) method by M.Pfreundshuh and coworkers.
Briefly, a cDNA from fresh tumor specimens is cloned
into phage expression vector. The recombinant proteins, which are expressed
during lytic infection of bacteria, are transferred onto nitrocellulose
membrane and then screened with autologous serum. Positive clones are identified,
verified, the inserts subcloned, and the nucleotide sequence of the cDNA
determined. These clones are then characterized for cancer-related profile
by serological analysis against panels of cancer and normal sera. We have
identified several novel and previously known gene products which appear
in these assays as putative cancer antigens. They include a novel homologue
of a component of telomerase complex, called tankyrase; human oncogene
cortactin (EMS-1), histone deacetylase, and several gene products whose
functions remains obscure. We also developed an assay for simultaneous
evaluation of multiple cancer antigens by serological screening.
Submitted manuscripts:
Human cortactin as putative
cancer antigen
TNKL, a tankyrase-like protein,
as a novel putative cancer antigen
Manuscript in preparation:
Simultaneous evaluation of
multiple cancer antigens using “large plaques” serological assay