Analysis of antigen to renal cell carcinoma and establishment of cancer specific antibody teratment

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Renal cell cancer (RCC) has a heterogeneous clinical presentation with up to 30% metastatic cases at initial diagnosis and 30% of initially organ-confined cases developing metastases during follow-up at variable intervals. Recently antibodies against specific molecules have been applied for clinical treatment to malignant diseases. Although several murine monoclonal antibodies (mAbs) which have been humanized became useful therapeutic agents against a few malignancies, therapeutic Abs are not yet available for the majority of the human cancers due to our lack of knowledge which antigens (Ags) can become useful targets. In the present study we established a procedure for comprehensive identification of such Ags through the extensive isolation of human mAbs that may become therapeutic. Using the phage-display Ab library we isolated a large number of human mAbs that bind to the surface of RCC cells. They were individually screened by immunostaining and clones that preferentially and strongly stained the malignant cells were chosen. The Ags recognized by those clones were isolated by immunoprecipitation and identified by mass spectrometry. We isolated 357 mAbs with unique sequences and identified 7 distinct. Ags highly expressed on several carcinomas. After preparing complete IgGi Abs the in vitro assay for antibody-dependent cell-mediated cytotoxicity (ADCC) and the in vivo assay in cancer-bearing athymic mice were performed to examine anti tumor activity. The mAbs converted to IgG1 revealed effective ADCC as well as and tumor activity in vivo. Thus, the procedure adopted in our study enabled us to succeed in comprehensive identification of tumor-associated antigens (TAAs) and simultaneous isolation of mAbs against RCC. Therefore, we believe that some Ags detected will be useful targets for cancer therapy and several mAbs will become useful therapeutic agents to RCC in the foreseeable future.