Kemp J D, Smith K M, Mayer J M, Gomez F, Thorson J A, Naumann P W
Department of Pathology, University of Iowa College of Medicine, Iowa City.
Pathobiology. 1992;60(1):27-32. doi: 10.1159/000163693.
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.
在肿瘤中制造缺铁状态的一种方法是将它们暴露于抗转铁蛋白受体单克隆抗体（抗转铁蛋白受体抗体）。本文回顾了抗转铁蛋白受体抗体的近期研究历程。多价（IgM或IgA）和二价（IgG）抗转铁蛋白受体抗体在体外和体内均表现出抗肿瘤活性，但IgG抗转铁蛋白受体抗体在与去铁胺等铁螯合剂联合使用或成对使用时似乎最为有效。为了理解以下几点，还需要更多信息：（1）抗转铁蛋白受体抗体自身以及与螯合剂联合使用时的作用方式；（2）抗转铁蛋白受体抗体在抑制效力方面彼此不同的原因；（3）抗转铁蛋白受体抗体是否能与其他抗肿瘤药物成功联合使用；以及（4）肿瘤对抗转铁蛋白受体抗体作用的敏感性为何存在显著差异。仅由抗转铁蛋白受体抗体治疗引起的缺铁毒性似乎不大，但只有进一步的体内实验和1期临床试验才能确定最新观察结果是否能转化为真正有用的治疗工具。
