Renal Cell Carcinoma Tumor Associated Antigen G250 (7,8,9)




    About 87% of RCC cells express the TAA G250, and the TAA is not expressed in normal tissues (7).   Patients with RCC also fail to demonstrate TIL specific activity towards the antigen. (8)
    Molecular analysis of the G250 has revealed it is identical to the cervical-carcinoma-associated antigen MN/CA IX, which some researches believe suggests that RCC could be caused by an unidentified HPV like virus. (9)

Out of 60 predicted peptide sequences, the following 18 have been shown to up-regulate HLA-A2.1 on T2 cells (8).
 
 


Vissers et al.: The Renal Cell Carcinoma-associated Antigen G250 Encodes a Human Leukocyte Antigen (HLA)-A2.1-restricted Epitope Recognized by Cytotoxic T Lymphocytes.  Cancer Research, 59: 5554-5559, 1999.




Vissers et al.: The Renal Cell Carcinoma-associated Antigen G250 Encodes a Human Leukocyte Antigen (HLA)-A2.1-restricted Epitope Recognized by Cytotoxic T Lymphocytes.  Cancer Research, 59: 5554-5559, 1999.
         To the left are the results of testing the immunogenicity of G250 peptide sequences in HLA-A2.1 Kb transgenic mice.  The mice used expressed the chimeric HLA-A2.1Kb molecule, in which the a-3 domain of the HLA-A2.1 molecule is replaced by the corresponding murine Kb a-3 domain, which results in a MHC molecule that can present peptides binding to the human HLA-2A.1 molecule and still interact with the CD8 molecule on murine T cells.
        Mice were vaccinated with the G250 derived peptides, and their spleen cells were restimulated in vitro for the cytotoxicity assay.  In the assay, EL-4/HLA-A2.1Kb cells loaded with the G250 derived peptides, were used to measue peptide specific lysis by CTLs.
        Of the thirteen tested, four induced CTL activity.
 

    Given the immunogenicity of G250 and high prevalence of this antigen in RCC patients, it makes for a potential target in developing Immunotherapies for RCC.
 
 



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