Cruzado Josep M, Bestard Oriol, Melilli Eduardo, Grinyó Josep M
Department of Nephrology, Hospital Universitari de Bellvitge, University of Barcelona, IDIBELL, L'Hospitalet de Llobregat , Barcelona, Spain.
Kidney Int Suppl (2011). 2011 Aug;1(2):47-51. doi: 10.1038/kisup.2011.12.
Although current immunosuppression is highly effective in avoiding acute rejection, it is associated with nephrotoxicity, cardiovascular morbidity, infection, and cancer. Thus, new drugs dealing with new mechanisms, as well as minimizing comorbidities, are warranted in renal transplantation. Few novel drugs are currently under investigation in Phase I, II, or III clinical trials. Belatacept is a humanized antibody that inhibits T-cell co-stimulation and has shown encouraging results in Phase II and III trials. Moreover, two new small molecules are under clinical development: AEB071 or sotrastaurin (a protein kinase C inhibitor) and CP-690550 or tasocitinib (a Janus kinase inhibitor). Refinement in selecting the best combinations for the new and current immunosuppressive agents is probably the main challenge for the next few years.
尽管目前的免疫抑制疗法在避免急性排斥反应方面非常有效,但它会引发肾毒性、心血管疾病、感染和癌症。因此,在肾移植中,开发具有新作用机制且能将合并症降至最低的新药是很有必要的。目前很少有新药处于I期、II期或III期临床试验研究阶段。贝拉西普是一种抑制T细胞共刺激的人源化抗体,已在II期和III期试验中显示出令人鼓舞的结果。此外,有两种新的小分子药物正在临床开发中:AEB071或索拉司他丁(一种蛋白激酶C抑制剂)以及CP-690550或托法替尼(一种Janus激酶抑制剂)。在未来几年,为新的和现有的免疫抑制剂选择最佳组合可能是主要挑战。