研究采用3～4 岁龄的食蟹猴，反复静脉或腹腔推注给予重组抗EpCAM

The study used 3 to 4 year-old cynomolgus monkeys to give recombinant anti-EpCAM (Epithelial cell adhesion molecule, epithelial cell adhesion molecule) and CD3 human-mouse chimeric bispecific antibody (M701) repeatedly intravenously or intraperitoneally. The administration was administered twice for 4 consecutive weeks, a total of 9 administrations, and a 4-week recovery period, to observe the toxic reaction and toxicokinetics of the test product to the cynomolgus monkey, the main toxic target organs, and the damage The degree of reversibility and the recovery of toxic reactions 4 weeks after the end of administration provide a reference for the design of clinical human doses and the monitoring of clinical toxic and side effects. A total of 50 cynomolgus monkeys were used in the experiment, half male and half male. Animal quarantine for 26 days, during which the animals were subjected to weight measurement, body temperature, ECG, blood pressure, eye examination, urine examination, hematology, blood coagulation and serum biochemical examination and clinical symptom observation. After the quarantine period is over, they are randomly divided into 5 experimental groups, namely the vehicle control group (special solvent: 0 mg/kg), the low-dose group (0.3 mg/kg), the medium-dose group (1 mg/kg), and the high-dose group. The group (3 mg/kg) and the intraperitoneal injection group (1 mg/kg) had 10 animals in each group, half of the male and the female. The above-mentioned low, medium and high doses are respectively about 91, 303, and 909 times the maximum proposed clinical dose (200μg/assumed 60 kg/person, approximately 3.3μg/kg). The route of administration is a slow bolus intravenously or intraperitoneally, and the administration volume is 10 mL/kg. During the experiment, observe the animal's clinical symptoms and injection site, measure body weight, food intake, body temperature, electrocardiogram, blood pressure, and perform urinalysis, ophthalmology, hematology, blood coagulation and serum biochemical tests. In the experimental group, 6 animals (half male and female) from each group were dissected on the 2nd day after the last administration, and the remaining 4 animals (half male and female) from each group were dissected after 4 weeks of recovery. At the same time, bone marrow smears were performed. The organs were weighed, and tissue samples were collected for histopathological examination. In addition, immunogenicity testing and cytokine testing are required. No serious adverse reactions caused by M701 were found in the study.

In this study, 3-4-year-old cynomolgus monkeys were repeatedly injected intravenously or intraperitoneally with recombinant anti EpCAM (epithelial cell adhesion molecule) and CD3 human mouse chimeric bispecific antibody (m701). They were administered twice a week for 4 weeks, a total of 9 times. A 4-week recovery period was set up to observe the toxic reaction and toxicokinetics of the test product on cynomolgus monkeys The main toxic target organs, the reversible degree of damage and the recovery of toxic reaction 4 weeks after administration provide a reference basis for the design of clinical human dose and the monitoring of clinical toxic and side effects. A total of 50 cynomolgus monkeys, half male and half female, were used in the experiment. The animals were quarantined for 26 days. During the period, the animals were measured for weight, body temperature, ECG, blood pressure, ophthalmic examination, urine examination, hematology, blood coagulation, serum biochemical examination and clinical symptom observation. After the quarantine period, they were randomly divided into five experimental groups: vehicle control group (special vehicle: 0 mg / kg), low dose group (0.3 mg / kg), medium dose group (1 mg / kg), high dose group (3 mg / kg) and intraperitoneal injection group (1 mg / kg). There were 10 rats in each group, half male and half female. The above low, medium and high doses were the maximum proposed clinical dose (200 mg / kg) μ G / assuming 60 kg / person, about 3.3 μ g/kg） During the experiment, the clinical symptoms and injection sites of the animals were observed, and the body weight, food intake, body temperature, ECG and blood pressure were measured. Urine examination, ophthalmology examination, hematology, blood coagulation and serum biochemical examination were carried out. Six animals were taken from each group on the second day after the last administration (half male and half female) dissection. After 4 weeks of recovery, the remaining 4 animals (half male and half female) in each group were dissected, bone marrow smears and organs were weighed, and tissue samples were collected for histopathological examination. In addition, immunogenicity test and cytokine test were also required. No serious adverse reactions caused by m701 were found in the study.<br>

In this study, cynomolgus monkeys aged 3-4 years were repeatedly injected intravenously or intraperitoneally with recombinant anti-EPCAM (epithelial cell adhesion molecule) and CD3 chimeric bispecific antibody (M701), twice a week, for 4 weeks, 9 times in total, with a 4-week recovery period. To observe the toxic reaction and toxicokinetics, the main toxic target organs, the reversible degree of damage and the recovery of toxic reaction 4 weeks after administration, so as to provide reference for the design of clinical human dose and the monitoring of clinical toxic and side effects. Fifty cynomolgus monkeys, half male and half female, were used in the experiment. The animals were quarantined for 26 days, during which they were given weight measurement, body temperature, ECG, blood pressure, eye examination, urine examination, hematology, blood coagulation, serum biochemical examination and clinical symptom observation. After the quarantine period, they were randomly divided into five experimental groups, namely solvent control group (special solvent: 0 mg/kg), low-dose group (0.3 mg/kg), medium-dose group (1 mg/kg), high-dose group (3 mg/kg) and intraperitoneal injection group (1 mg/kg), with 10 rats in each group, half male and half female. The above-mentioned low, medium and high doses are about 91, 303 and 909 times of the maximum clinical dose (200μg/ 60 kg/ person, about 3.3μg/kg). The administration route was intravenous or intraperitoneal slow push injection, and the administration volume was 10 mL/kg. During the experiment, the clinical symptoms and injection sites of animals were observed, and the body weight, food intake, body temperature, ECG and blood pressure were measured. Urine examination, ophthalmological examination, hematology, blood coagulation and serum biochemical examination were carried out. In the experimental group, 6 animals (half male and half female) were dissected in each group on the 2nd day after the last administration, and the remaining 4 animals (half female and half male) were dissected in each group after 4 weeks of recovery period. Meanwhile, bone marrow smear and organ weighing were performed, and tissue samples were collected for histopathological examination. In addition, immunogenicity test and cytokine test are needed. No serious adverse reactions caused by M701 were found in the study.