Biopolym. Cell. 2004; 20(1-2):151-157.
http://dx.doi.org/10.7124/bc.0006A1
Allogenic screening of tumor antigens from thyroid cancer cDNA libraries
1Kyyamova R. G., 1Rodnin N. V., 1Garifulin O. M., 1Tykhonkova I. O., 2Koroleva E. P., 3Malets M. S., 1, 4Gout I. T., 1Filonenko V. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
    32, Vavilova Str., Moscow, Russian Federation, 119991
  3. Kiev oncological hospital
    67, Verhovynna Str., Kyiv, Ukraine, 03115
  4. Ludwig Institute for Cancer Research
    91 Riding house str., London, UK, WIP8BT

Abstract

The search for novel tumor-associated antigens eliciting humoral and cellular immune responses in tumor patients is an important goal in cancer diagnosis and immunotherapy. We utilized SEREX immunoscreening methodology to identify a set of novel tumor antigens, associated with thyroid cancer. 16 distinct antigens reactive with autologous sera were identified by SEREX analysis of two cDNA libraries from patients with papillar carcinoma of thyroid gland. SEREX-defined antigens were evaluated by allogenic screening with sera samples from normal donors, patients with thyroid, colon and breast cancer. The analysis showed that 8 antigens reacted exclusively with autologous sera, 2 antigens (KY-THY-25 and KY-THY-40) were recognized by sera from patients with thyroid and breast cancer (10 % and 2.4 % respectively) while the other antigens cross-reacted with the sera from both normal donors and cancer patients. KY-THY-17 (zinc finger protein), KY-THY-28 (transducer of ERBB2) and KY-THY-29 (solid tumor associated protein) exhibited high immunoreactivity with sera from patients with thyroid, breast and colon cancer, when compared with the sera from normal donors. These antigens are potential candidates for the development of novel diagnostic and immunotherapeutic approaches in cancer.
Full text: (PDF, in Ukrainian)

References

[1] Jager D, Jager E, Knuth A. Immune responses to tumour antigens: Implications for antigen specific immunotherapy of cancer. J Clin Pathol. 2001;54(9):669-74.
[2] Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A. 1995;92(25):11810-3.
[3] Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: An expanding family of targets for cancer immunotherapy. Immunol Rev. 2002;188:22-32.
[4] Jager E, Chen YT, Drijfhout JW, Karbach J, Ringhoffer M, Jager D, Arand M, Wada H, Noguchi Y, Stockert E, Old LJ, Knuth A. Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: Definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes. J Exp Med. 1998;187(2):265-70.
[5] Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156-9.
[6] Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Tureci O, Sahin U, Pfreundschuh M, Old LJ. Characterization of human colon cancer antigens recognized by autologous antibodies. Int J Cancer. 1998;76(5):652-8.
[7] Rodnin N. V., Tykhonkova I. O., Nemazany I. O., Gorlova L. M., Komissarenko I.V., Palchevskiy S. S., Kuharenko O. P., Drobot L. B., Matsuka G. H., Filonenko V. V., Gout I. T. Serological identification of autoimmune reactive antigenes in human thyroid cancer cells. Exp. oncol. 2000; 22(3):135-138.
[8] Rodnin N.V., Tykhonkova I.O., Kyyamova R.G., Garifulin O.M., Gout I.T., Filonenko V.V. Identification of tumor-associated antigens in human thyroid papillar carcinoma. Biopolym. Cell, 2003 19 (6):541-547.
[9] Waghray A, Keppler D, Sloane BF, Schuger L, Chen YQ. Analysis of a truncated form of cathepsin H in human prostate tumor cells. J Biol Chem. 2002;277(13):11533-8.
[10] Rae FK, Hooper JD, Nicol DL, Clements JA. Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors. Mol Carcinog. 2001;32(1):44-53.
[11] Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jager D, Jager E, Knuth A, Chen YT, Old LJ. Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int J Cancer. 1999;83(4):456-64.
[12] Koroleva EP, Lagarkova MA, Mesheryakov AA, Scanlan MJ, Old LJ, Nedospasov SA, Kuprash DV. Serological identification of antigens associated with renal cell carcinoma. Russ J Immunol. 2002;7(3):229-38.
[13] Stephen RL, Crabtree JE, Yoshimura T, Clayton CL, Dixon MF, Robinson PA. Increased zinc finger protein zFOC1 transcripts in gastric cancer compared with normal gastric tissue. Mol Pathol. 2003;56(3):167-71.
[14] Ferbus D, Flechon A, Muleris M, Li Y, Hanash S, Terris B, Hammel P, Pibouin L, Dutrillaux B, Goubin G. Amplification and over-expression of OZF, a gene encoding a zinc finger protein, in human pancreatic carcinomas. Int J Cancer. 1999;80(3):369-72.
[15] Ferbus D, Bovin C, Validire P, Goubin G. The zinc finger protein OZF (ZNF146) in overexpressed in colorectal cancer. J Pathol. 2003;200(2):177-82.
[16] Ikematsu N, Yoshida Y, Kawamura-Tsuzuku J, Ohsugi M, Onda M, Hirai M, Fujimoto J, Yamamoto T. Tob2, a novel anti-proliferative Tob/BTG1 family member, associates with a component of the CCR4 transcriptional regulatory complex capable of binding cyclin-dependent kinases. Oncogene. 1999;18(52):7432-41.
[17] Matsuda S, Kawamura-Tsuzuku J, Ohsugi M, Yoshida M, Emi M, Nakamura Y, Onda M, Yoshida Y, Nishiyama A, Yamamoto T. Tob, a novel protein that interacts with p185erbB2, is associated with anti-proliferative activity. Oncogene. 1996;12(4):705-13.
[18] Khanson KP, Imianitov EN. ERBB2/HER2: from molecular to clinical oncology. Vopr Onkol. 2002;48(2):137-45.