| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
One of the larger concernsin melanoma T cell based immunotherapy is the immune escape phenomenon resulting from loss of melanoma associated antigens and/or HLA class I. The head investigator has been analyzing the mechanisms of down regulation of HLA class I in melanocytic cells.
HLA class I was down regulated in melanoma lesions, which results in no T cell infiltration in such lesions. Theoretically loss of HLA class I in melanoma cells allows NK cell infiltration. However, most of the melanoma lesions show neither T cell nor NK cell infiltration. These data suggest that melanoma cells can escape from NK cell attack.
In the present study, analysis of immune escape from NK cell in melanoma was investigated using monoclonal antibodies to MHC class I chain-related molecule A and B (MICA and MICB), which are ligands for the newly cloned NK cell activating receptor NKG2D.
The head investigator found the following points :
1)Expression of MICA in culture human melanoma cell lines
Ten of 16 human
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melanoma cell lines were shown to be MICA positive by ELISA.
2)Expression of MICA in melanocytic tumors
Expression of MICA in melanocytic lesions was investigated immunohistochemically using frozen melanocytic nevus, and primary and metastatic melanoma lesions. MICA was not expressed in melanocytic nevus, however it was expressed in melanoma lesions. MICA was expressed in 30%, 60%, and 20% of radial growth phase, vertical growth phase, and metastatic lesions, respectively.
3)Selection of monoclonal antibody to MICB which can react with formalin-fixed tissue section
The monoclonal antibody to MICA did not react with formalin-fixed tissue sections. Therefore, I tried to find a monoclonal antibody to MICB which can react with formalin-fixed tissue section from more than 10 antibodies to MICB. We were able to select one antibody to MICB that could react with formalin-fixed tissue sections using the retrieval antigen method.
These data will facilitate the analysis of immune escape from NK cell in melanoma and further research project is under going at my laboratory. Less
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