Development of humanized antibodies as cancer therapeutics.
Recent success in the development of monoclonal antibody-based anti-cancer drugs has largely benefitted from the advancements made in recombinant technologies and cell culture production. These reagents, derived from the antibodies of mouse origin, while maintaining the exquisite specificity and affinity to the tumor antigens, have low immunogenicity and toxicity in human. High-level expressing cell clones are generated and used to produce large quantities of the recombinant antibodies in bioreactors in order to meet the clinical demand for therapeutic applications. In this report, the systems and general methodologies developed by us to construct and produce humanized antibodies from the parent mouse antibodies are described. Once the humanized antibodies are available, they can be applied in three principal forms for cancer therapy: (1) naked antibodies, (2) drug- or toxin conjugates, and (3) radioconjugates. Using the humanized anti-CD22 (epratuzumab) and anti-carcinoembryonic antigen (ant-CEA; labetuzumab) antibody prototypes, clinical applications of naked and radiolabeled humanized monoclonal antibodies are described.
Qu
Zhengxing
Z
Immunomedics, Inc., Morris Plains, NJ 07950, USA. tqu@immunomedics.com
Griffiths
Gary L
GL
Wegener
William A
WA
Chang
Chien-Hsing
CH
Govindan
Serengulam V
SV
Horak
Ivan D
ID
Hansen
Hans J
HJ
Goldenberg
David M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; C448700:epratuzumab