Development of molecular targeting therapy using nuclear-transpoted humanized monoclonal antibody

CD 26存在于各种癌症的细胞表面。结果表明，人源化抗CD 26单克隆抗体（Ab）抑制癌细胞生长，Ab处理诱导CD 26和YS 110的核转位。在抗体处理的反应，它被揭示与POLR 2A基因的基因组侧翼区，RNA聚合酶II的亚基，使用染色质免疫沉淀试验的核CD 26相互作用。这种与核CD 26和POLR 2A基因的相互作用导致POLR 2A基因的转录抑制，导致癌细胞的细胞增殖延迟。将抗癌试剂X与Ab偶联，结果表明，X-Ab对癌细胞的生长有明显的抑制作用。结果表明，Ab和X-Ab对正常人内皮细胞和表达CD 26的T淋巴细胞的生长无明显影响。与Ab治疗相比，X-Ab治疗显著减少了异种移植的人癌。

CD26 is on cell surface of various types of cancers. It was shown humanized anti-CD26 monoclonal antibody(Ab) inhibited cancer cell growth and the Ab treatment induced nuclear translocation of both CD26 and YS110. In response to Ab treatment, it was revealed nuclear CD26 interacted with a genomic flanking region of POLR2A gene, a subunit of RNA polymerase II, using a chromatin immunoprecipitation assay. This interaction with nuclear CD26 and POLR2A gene consequently led to transcriptional repression of the POLR2A gene, resulting in retarded cell proliferation of cancer cells. Anti-cancer reagent X was conjugated with Ab, as a result X-Ab inhibited severely cancer cell growth as compaired with Ab only. It was revealed that Ab or X-Ab did not impair cell growth of normal human endothelial cell and T lymphocyte with CD26 expression. Xenografted human carcinomas were reduced significantly by X-Ab treatment as compared with Ab treatment.