Molecular cloning and immunogenicity of renal cell carcinoma‐associated antigen G250

The molecular cloning of the cDNA and gene encoding the renal cell carcinoma (RCC)‐associated protein G250 is described. This protein is one of the best markers for clear cell RCC: all clear‐cell RCC express this protein, whereas no expression can be detected in normal kidney and most other normal tissue. Antibody studies have indicated that this molecule might serve as a therapeutic target. In view of the induction/up‐regulation of G250 antigen in RCC, its restricted tissue expression and its possible role in therapy, we set out to molecularly define the G250 antigen, which we identified as a transmembrane protein identical to the tumor‐associated antigen MN/CAIX. We determined, by FISH analysis, that the G250/MN/CAIX gene is located on chromosome 9p12‐13. In view of the relative immunogenicity of RCC, we investigated whether the G250 antigen can be recognized by TIL derived from RCC patients. The initial characterization of 18 different TIL cultures suggests that anti‐G250 reactivity is rare. Int. J. Cancer 85:865–870, 2000. © 2000 Wiley‐Liss, Inc.

[1]  C. Auffray,et al.  Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. , 2005, European journal of biochemistry.

[2]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[3]  S. Larson,et al.  Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[4]  S. Fleming.  Genetics of kidney tumours. , 1998, Forum.

[5]  M. Stifelman,et al.  Expression of the tumor-associated gene MN: a potential biomarker for human renal cell carcinoma. , 1997, Cancer research.

[6]  W. Linehan,et al.  Allelic deletions of the VHL gene detected in multiple microscopic clear cell renal lesions in von Hippel-Lindau disease patients. , 1996, The American journal of pathology.

[7]  R. Kettmann,et al.  Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. , 1996, Genomics.

[8]  V. Moreno,et al.  Prevalence of Human Papillomavirus in Cervical Cancer: a Worldwide Perspective , 1995 .

[9]  J. Schalken,et al.  The use of monoclonal antibody G250 in the therapy of renal-cell carcinoma. , 1995, Seminars in oncology.

[10]  R. Kettmann,et al.  Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. , 1994, Oncogene.

[11]  F. Debruyne,et al.  Vaccination with ant‐idiotype antibodies mimicking a renal cell carcinoma‐associated antigen induces tumor immunity , 1994, International journal of cancer.

[12]  R. Brakenhoff,et al.  Optimization and simplification of expression cloning in eukaryotic vector/host systems. , 1994, Analytical biochemistry.

[13]  C. Figdor,et al.  Melanocyte lineage-specific antigen gp100 is recognized by melanoma- derived tumor-infiltrating lymphocytes , 1994, The Journal of experimental medicine.

[14]  G. Riethmüller,et al.  Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines. , 1993, Journal of immunology.

[15]  B. Gansbacher,et al.  Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes: modulation of recognition through retroviral transduction of tumor cells with interleukin 2 complementary DNA and exogenous alpha interferon treatment. , 1993, Cancer research.

[16]  N. Bander,et al.  Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  R. V. van Lier,et al.  T cell receptor/CD3 and CD28 use distinct intracellular signaling pathways , 1991, European journal of immunology.

[18]  M. Kozak.  The scanning model for translation: an update , 1989, The Journal of cell biology.

[19]  D. Ruiter,et al.  Monoclonal antibody G 250 recognizes a determinant present in renal‐cell carcinoma and absent from normal kidney , 1986, International journal of cancer.

[20]  G. Shaw,et al.  A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation , 1986, Cell.

[21]  R. Vessella,et al.  Monoclonal antibodies to human renal cell carcinoma: recognition of shared and restricted tissue antigens. , 1985, Cancer research.

[22]  B. Hoffman,et al.  A simple and very efficient method for generating cDNA libraries. , 1983, Gene.

[23]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[24]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[25]  F. Waldman,et al.  Genetic aberrations detected by comparative genomic hybridization are associated with clinical outcome in renal cell carcinoma. , 1996, Cancer research.

[26]  A. Belldegrun,et al.  Interleukin 2 expanded tumor-infiltrating lymphocytes in human renal cell cancer: isolation, characterization, and antitumor activity. , 1988, Cancer research.