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.