MAGE-A3癌症免疫治疗药物（一种用于癌症治疗的治疗性疫苗）的非临床生殖和发育安全性评估。
Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment.
作者信息
Destexhe E, Stannard D, Wilby O K, Grosdidier E, Baudson N, Forster R, Gérard C M, Garçon N, Segal L
机构信息
GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium.
Huntingdon Life Sciences, Eye Research Centre, Eye, Suffolk IP23 7PX, UK.
出版信息
Reprod Toxicol. 2015 Jan;51:90-105. doi: 10.1016/j.reprotox.2014.12.009. Epub 2014 Dec 18.
We assessed potential toxic effects of the MAGE-A3 Cancer Immunotherapeutic on female fertility and embryo-fetal, pre- and post-natal development in rats and on male fertility in rats and monkeys. Three groups of 48 female (Study 1) or 22 male (Study 2) CD rats received 5 or 3 injections of 100μL of saline, AS15 immunostimulant, or MAGE-A3 Cancer Immunotherapeutic (MAGE-A3 recombinant protein combined with AS15) at various timepoints pre- or post-mating. Male Cynomolgus monkeys (Study 3) received 8 injections of 500μL of saline (n=2) or the MAGE-A3 Cancer Immunotherapeutic (n=6) every 2 weeks. Rats were sacrificed on gestation day 20 or lactation day 25 (Study 1) or 9 weeks after first injection (Study 2) and monkeys, 3 days or 8 weeks after last injection. Injections were well tolerated. Female rat mating performance or fertility, pre- and post-natal survival, offspring development up to 25 days of age, and male mating performance (rats) or fertility parameters (rats and monkeys) were unaffected.
我们评估了MAGE - A3癌症免疫疗法对雌性大鼠生育能力、胚胎 - 胎儿及产前和产后发育的潜在毒性作用，以及对雄性大鼠和猴子生育能力的潜在毒性作用。三组48只雌性（研究1）或22只雄性（研究2）CD大鼠在交配前或交配后的不同时间点接受5次或3次100μL生理盐水、AS15免疫刺激剂或MAGE - A3癌症免疫疗法（MAGE - A3重组蛋白与AS15联合）注射。雄性食蟹猴（研究3）每2周接受8次500μL生理盐水（n = 2）或MAGE - A3癌症免疫疗法（n = 6）注射。大鼠在妊娠第20天或哺乳期第25天（研究1）或首次注射后9周（研究2）处死，猴子在最后一次注射后3天或8周处死。注射耐受性良好。雌性大鼠的交配性能或生育能力、产前和产后存活率、25日龄前的后代发育，以及雄性大鼠的交配性能（大鼠）或生育参数（大鼠和猴子）均未受影响。
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