ABSTRACT
Antibody-drug conjugates (ADCs) are widely used in cancer treatment. Human epidermal growth factor receptor-2 (HER2) is overexpressed in various types of solid tumors and is a validated therapeutic target for cancers. To develop a more effective therapy, we generated a novel anti-HER2 humanized monoclonal antibody MIL40 and MIL40 drug conjugates as novel cancer therapies. The MIL40 was conjugated with small molecule cytotoxic agents DM1 [emtansine, N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine] or monomethylauristatin E (MMAE) to generate ADCs, which were evaluated for their in vitro and in vivo anti-cancer activities. Experimental results show that MIL40-DM1 and MIL40-MMAE can effectively identify and bind to HER2-positive tumor cells. The binding capabilities of MIL40-DM1 and MIL40-MMAE with HER2 extracellular domain (ECD) antigens were not different after conjugation with DM1 or MMAE. The ADCs showed potent cytotoxicity in HER2-positive ovarian cancer cells SKOV3, breast cancer cells SKBR3 and stomach cancer cells N87 in vitro. MIL40-DM1 can effectively inhibit the volume and weight growth of SKOV3 transplant tumors in mice. The mice in this study were used and treated by following the international guidelines for the care and use of laboratory animals, and approved by Animal Ethics Committee of Institute of Military Cognitive and Brain Sciences.
ABSTRACT
The folate receptor is highly selective tumor marker overexpressed in epithelioid cancer cells. As a targeting method ,folic acid mediated nanoscale drug delivery system has the advantages of folate-folate receptor's active targeting and nanoscale drug delivery's passive targeting. Active and passive targeting enable nanoscale drug delivery system release drugs in the location of tumor, which increases therapeutic index of drug and cuts down its side effect. In this article, we review folate-liposome , folate-dendrimer, folate-micelle, folate-nanophere and other folate receptor mediated tumor-targeting nanoscale drug delivery systems. Compared to traditional preparations, the novel nanoscale drug delivery system may offer a very promising approach for tumor-targeting therapy.