Folate receptor targeted drug delivery- from the bench to the bedside

Jing Xie, Zhou Chen, Aili Zhang, Bin Zheng, Shuang Yang, Lesheng Teng


Targeted drug delivery is a promising strategy for improving tumor therapy. Folate receptor (FR) is an established ovarian cancer marker that is also frequently found to be overexpressed in other major epithelial tumors. Meanwhile, functional FR−β is expressed in myeloid leukemias and in inflammatory macrophages, including tumor-associated macrophages. FR based tumor targeted drug delivery has been a very active area of research and recent advancement of this technology towards clinical translation is highly significant. FR targeting can be achieved via anti-FR antibody or by folate conjugation, each with distinctive advantages and pitfalls. Several monoclonal antibodies directed against FR−α have been developed. In addition, a large number of imaging agents, drug molecules, and drug carriers have been conjugated to folate for targeting the FR, mostly for targeting FR−α found on the surface of epithelial tumor cells. Only recently, however, have FR-targeted agents moved into Phase III clinical trials, exemplified by the monoclonal antibody farletuzumab and the low molecular weight folate conjugates, folate-99mTc (EC20) and folate-desacetylvinblastinehydrazide (EC145), representing each of the two competing strategies for targeting the FR. This review will focus on the activities related to clinical translation of FR-targeted agents. The reader will gain a better understanding of the landscape of clinical translation of this exciting technology and key findings in the clinical trials. The anticipated approval of these agents and the ongoing clinical development of several other folate conjugates should usher in a new era of clinical translation and validation of FR-targeted imaging and therapeutic agents for tumor imaging and therapy.


Folate receptor; cancer; leukemia; targeted drug delivery; liposomes.

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