抗肿瘤多肽HM-3的中和抗体活性研究

Research of anti-tumor peptide neutralizing antibodies activities

本研究检测抗肿瘤多肽HM-3在SD大鼠和食蟹猴长期毒性实验血清中中和抗体的产生及抗体活性的强弱。将SD大鼠与食蟹猴分别分成4.5,13.5,40.5mg/kg和3,9,27mg/kg3个剂量组,均每日静脉注射HM-3多肽1次,均连续给药6个月。每月取血清用ELISA法测定滴度,并用细胞迁移法测定抗体中和活性。长期给药过程中,中高剂量组的SD大鼠能产生抗体,其中少数检测到中和抗体的活性(P<0.05),而食蟹猴中能产生抗体的数量较少,且其中只有个别食蟹猴的血清中能检测到中和抗体的产生(P<0.05)。且抗体滴度与中和抗体活性不呈正相关。由此,本研究认为HM-3的抗原性较低,长期高剂量给药后极个别会产生一些低亲和力的中和抗体。

The generation and activity of serum neuralizing antibody in cynomolgus monkeys and SD rats undergoing long-term toxicity study with antitumor peptides HM-3 were investigated.The rats were administered intravenously with HM-3 at doses of 4.5 mg/kg,13.5 mg/kg,and 40.5 mg/kg for 6 months,and the cynomolgus monkeys were administrated intravenously with HM-3 at doses of 3 mg/kg,9 mg/kg and 27 mg/kg for 6 months,respectively.Anti-HM-3 antibodies and their neutralizing activities in serum samples taken every month after the administrations were determined by ELISA and cell migration assay,respectively.During the long-term administrations,anti-HM-3 antibodies were generated in some SD rats at high and moderate dose groups,and the anti-body-neutralizing activities could be detected in a number of these samples （P〈0.05）.However,activity could be detected in very few monkeys （P〈0.05）,and the antibody titers were not correlated with the neutralizing activities.Therefore,we conclude that the antigenicity of HM-3 was low,but after long-term administration at high dose,low affinity neutralizing antibody could be generated in small number of samples.