ヒト腎癌に対するマウスモノクローナル抗体mAb K2.7による腎癌特異的抗腫瘍免疫活性

Abstract

1)IgG3isotypeであるmAb K2.7は腎癌原発巣および転移巣の92%の症例と反応した。2)健常人からの血清およびPBLにてmAb K2.7はCDCとADCCを介して腎癌細胞株を殺した。3)腎癌9例からの血清およびPBLも健常人と同程度のCDCとADCC活性を認めた。4)腎癌の臨床病期に関係なく, すべての腎癌患者に抗腫瘍活性を認めた。5)抗腫瘍活性は腎癌細胞株の細胞表面上の抗原量に相関した

We have prepared a mouse monoclonal antibody (mAb) K2.7 (IgG3) by immunizing mice with renal cancer cell (RCC) line OS-RC-2. In a serological analysis by protein A assay, 25 out of 31 RCC lines reacted with the mAb K2.7 but none of the 50 other cell lines from different organs except for 2 cell lines did. In immunohistological analysis by indirect immunoperoxidase assay, 66 out of 72 renal cancer tissues showed positive staining. Metastatic lesions of renal cancers also reacted similarly to the primary lesion. Some restricted normal tissues including tubules of normal kidney showed positive staining. Specific antitumor activities of mAb K2.7 against RCC lines were investigated in vitro by complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC) assays. In CDC assay, all of the 9 RCC lines were killed by mAb K2.7 and normal human serum, and killing activities of mAb K2.7 presumably depend on the number of antibody molecules bound to the cell surface. Sera from 9 patients with renal cancers including low and high stages showed the same killing activities to 3 RCC lines as normal human serum. In the ADCC assay, peripheral leukocytes (PBLs) from 4 healthy donors showed strong killing activities to RCC lines. Killing activity differed with the individual. PBLs from the same 9 patients as in the CDC assay showed significantly positive killing activity against 3 RCC lines. These findings suggest the usefulness of mAb K2.7 for the specific immunotherapy of renal cancer.