Effects of anti-transferrin receptor antibodies on the growth of neoplastic cells.
One approach to creating a state of iron deprivation in tumors is to expose them to monoclonal antibodies against the transferrin receptor (ATRAs). This paper reviews the recent history of studies with ATRAs. Both multivalent (IgM or IgA) and bivalent (IgG) ATRAs exhibit anti-tumor activity in vitro and in vivo, but IgG ATRAs appear to be most effective when used with an iron chelator such as deferoxamine or when used in pairs. Much more information is needed in order to understand: (1) how ATRAs work by themselves and in conjunction with chelators; (2) why ATRAs differ from one another in terms of their inhibitory potency; (3) whether ATRAs can be used successfully in conjunction with other anti-tumor agents, and (4) why tumors exhibit marked differences in their sensitivity to the effects of ATRAs. The toxicity of iron deprivation arising from ATRA treatment alone seems modest, but only further experimental work in vivo and in phase-1 clinical trials can determine whether the most recent observations can be converted into truly useful therapeutic tools.
Kemp
J D
JD
Department of Pathology, University of Iowa College of Medicine, Iowa City.
Smith
K M
KM
Mayer
J M
JM
Gomez
F
F
Thorson
J A
JA
Naumann
P W
PW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006801:Humans; D007501:Iron / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors* / Q000276:immunology
D000911:Antibodies, Monoclonal; D011990:Receptors, Transferrin; D007501:Iron