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

CD26在各种类型的肿瘤细胞表面均有表达。人源化抗CD26单抗抑制肿瘤细胞生长，诱导CD26和YS110核移位。通过染色质免疫沉淀分析，发现核CD26与RNA聚合酶II的一个亚单位POLR2A基因的侧翼区相互作用。这种与核CD26和POLR2A基因的相互作用导致了POLR2A基因的转录抑制，从而抑制了癌细胞的增殖。抗癌剂X与单抗偶联，与单抗相比，X-单抗对癌细胞生长的抑制作用更强。结果表明，单抗和X-单抗对正常人内皮细胞和表达CD26的T淋巴细胞的生长无明显影响。与单抗治疗相比，X-Ab治疗明显减少了移植瘤的数量。

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.