Huo Yan, Li Bo, Zhang Yingqi, Wang Sanlong, Bao Musheng, Gao Xin, Li Dapeng, Wang Liying, Yu Yongli, Wang Junzhi
Biotechnology Center, School of Pharmacy, The Fouth Military Medical University, Xi'an, China.
Regul Toxicol Pharmacol. 2007 Oct;49(1):63-74. doi: 10.1016/j.yrtph.2007.05.005. Epub 2007 May 26.
With a goal of developing a medication for the treatment of MUC1 expressing human cancers, a recombinant heat shock protein 65-MUC1 fusion protein (HSP65-MUC1) between BCG derived heat shock protein 65 (HSP65) and MUC1 derived peptide (MUC1) was developed. To move the HSP65-MUC1 into a phase I clinical trial, a comprehensive non-clinical safety evaluation was conducted. The evaluation comprised of single-dose toxicity and repeat-dose toxicity studies both in mice and rhesus monkeys. The data from the study indicates that the treatment with HSP65-MUC1 is not associated with obvious toxicity in the tested animals. The changes in clinical chemistry and hematology in both the mice and monkeys were considered to be mild because there were no indications of overt toxicity after administering HSP65-MUC1. The data provided here contributed to the approval of initiating a phase I clinical trial with HSP65-MUC1 for the treatment of patients with MUC1-positive breast cancer in China.
为研发一种用于治疗表达MUC1的人类癌症的药物，构建了一种卡介苗来源的热休克蛋白65（HSP65）与MUC1来源肽（MUC1）之间的重组热休克蛋白65-MUC1融合蛋白（HSP65-MUC1）。为将HSP65-MUC1推进到I期临床试验，开展了全面的非临床安全性评估。该评估包括在小鼠和恒河猴身上进行的单剂量毒性和重复剂量毒性研究。研究数据表明，HSP65-MUC1治疗在受试动物中未显示明显毒性。小鼠和猴子的临床化学和血液学变化被认为是轻微的，因为给予HSP65-MUC1后没有明显毒性迹象。此处提供的数据有助于批准在中国启动HSP65-MUC1治疗MUC1阳性乳腺癌患者的I期临床试验。
