Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment

Reprod Toxicol. 2015 Jan:51:90-105. doi: 10.1016/j.reprotox.2014.12.009. Epub 2014 Dec 18.

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.

Keywords: Cancer immunotherapy; Immunostimulant; Monkey; Rat; Reproductive toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / blood
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / pharmacology*
  • Embryonic Development / drug effects*
  • Female
  • Fertility / drug effects*
  • Fetal Development / drug effects*
  • Immunotherapy
  • Macaca fascicularis
  • Male
  • Neoplasm Proteins / immunology*
  • Rats
  • Reproduction / drug effects*

Substances

  • Antibodies
  • Antigens, Neoplasm
  • Cancer Vaccines
  • MAGEA3 protein, human
  • Neoplasm Proteins