Relevance, advantages and limitations of animal models used in the development of monoclonal antibodies for cancer treatment.
Antibody humanisation through recombinant DNA technology was a key step in allowing monoclonal antibodies (mAbs) to reach the clinic, particularly for the treatment of cancer. As a consequence, they are less adapted to animal studies, although these studies continue to be important tools to study antibody distribution and action at the level of a whole organism. Moreover, preclinical studies in animals are mandatory before the approval of biologics license applications for mAbs by the U.S. Food and Drug Administration (FDA) or European Agency for the Evaluation of Medicinal Products (EMEA). Different parameters should be taken in consideration before starting animal experiments with recombinant mAbs, including antibody cross-reactivity, immunogenicity, pharmacokinetics, and possible interactions with the host immune system. The various interspecies differences are reviewed and discussed in light of the pharmacological properties expected in patients. In doing so, this article aims to provide a critical review of the animal models used in preclinical studies of mAbs for cancer treatment. In particular, their relevance, advantages and limitations will be discussed.
Loisel
Severine
S
Université de Bretagne Occidentale, Laboratoire de Thérapie Cellulaire et d'Immunobiologie du Cancer, EA 2216, 29609 Brest Cedex, France. severine.loisel@univ-brest.fr
Ohresser
Marc
M
Pallardy
Marc
M
Daydé
David
D
Berthou
Christian
C
Cartron
Guillaume
G
Watier
Hervé
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000918:Antibody Specificity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm