title: Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment.
abstract: 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.
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Destexhe
authors.affiliation: Huntingdon Life Sciences, Eye Research Centre, Eye, Suffolk IP23 7PX, UK.
authors.forename: D
authors.initials: D
authors.lastname: Stannard
authors.affiliation: Huntingdon Life Sciences, Eye Research Centre, Eye, Suffolk IP23 7PX, UK.
authors.forename: O K
authors.initials: OK
authors.lastname: Wilby
authors.affiliation: CiToxLAB France, BP 563, 27005 Evreux, France.
authors.forename: E
authors.initials: E
authors.lastname: Grosdidier
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Baudson
authors.affiliation: CiToxLAB France, BP 563, 27005 Evreux, France.
authors.forename: R
authors.initials: R
authors.lastname: Forster
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: C M
authors.initials: CM
authors.lastname: Gérard
authors.affiliation: Bioaster, 321 Avenue Jean Jaurès, 69007 Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Garçon
authors.affiliation: GSK Vaccines, Parc de la Noire Epine, Rue Fleming 20, 1300 Wavre, Belgium. Electronic address: LAWRENCE.M.SEGAL@GSK.COM.
authors.forename: L
authors.initials: L
authors.lastname: Segal
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000494:pharmacology*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D047109:Fetal Development / Q000187:drug effects*; D007167:Immunotherapy; D008252:Macaca fascicularis; D008297:Male; D009363:Neoplasm Proteins / Q000276:immunology*; D051381:Rats; D012098:Reproduction / Q000187:drug effects*
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins
keywords: Cancer immunotherapy; Immunostimulant; Monkey; Rat; Reproductive toxicity