Department of Molecular Immunology

Main results:

Cancer serology. Serological screening of expression cDNA libraries from renal, breast, ovarian and colon cancers and from cancer cell lines and normal testis (approximately 2000000 clones tested, out of which 443 serologically positive clones were submitted to Cancer Immunome Database, SEREX project). Three novel human cancer antigens discovered, and seven previously described proteins shown to be putative cancer antigens [Lagarkova et al., 2000; Lagarkova et al., 2003; Kuimov et al., 2001; Shebzukhov et al., 2005a, Shebzukhov et al., 2005b]. We developed an improved method to detect serological responses to tumor-associated antigens using a panel of cancer-specific antigens for serologic diagnostics and monitoring of melanoma, renal cancer, breast cancer, ovary cancer, lung cancer and colon cancer. It allowed simultaneous detection of responses to multiple antigens. New version of the method utilizes recombinant proteins purified by chromatography. A library of clinical specimens (blood serum samples and tissue specimens from patients with different cancers) characterized by panel of cancer-specific antigens was collected.

Physiological functions of TNF and LT. A unique panel of mice with complete and tissue-specific inactivation of tumor necrosis factor (TNF) and lymphotoxin (LT) genes was generated. Our data revealed distinct functions for LT produced by B-lymphocytes [Tumanov et al., 2002] and for TNF produced by macrophages and T-cells [Grivennikov et al., 2005], and demonstrated cooperation of TNF and LT in vivo [Kuprash et al., 2002]. Molecular mechanism of the action of cyclosporin A on expression of LTα gene was established [Kuprash et al., 2002]. Mouse monoclonal antibodies against genetically cloned TNF were sequenced [Radko et al., Russ. J. Immunol. 7: 371, 2002] and used for generation of bioengineered TNF inhibitor. A novel animal model for studing the consequences of TNF blockade in vivo has been generated: mice with “humanized” TNF/LT locus.