Enhanced cytotoxicity of monoclonal anticancer antibody 2C5-modified doxorubicin-loaded PEGylated liposomes against various tumor cell lines

Doxorubicin-loaded long-circulating liposomes (Doxil(TM), ALZA Corp.) were additionally modified with the nucleosome-specific monoclonal antibody 2C5 (mAb 2C5) recognizing a broad variety of tumor cells via the tumor cell surface-bound nucleosomes. These mAb 2C5-modified PEGylated liposomes demonstrated 3-8-fold increase in the in vitro binding and internalization by multiple cancer cell lines of diverse origins (murine LLC, 4T1, C26 and human BT-20, MCF-7, and PC3), as shown by flow cytometry (FACS) and epi and confocal microscopy As a result, mAb 2C5-modified Doxil(TM) demonstrated significantly higher cytotoxicity towards various cancer cells, including those resistant to doxorubicin, than all control preparations. The specific internalization of the mAb 2C5-Doxil(TM) into cytosol, along with the nuclear localization of their drug load, inside the target cancer cells were mainly responsible the superior anticancer activity The IC50 values of mAb 2C5-Doxil(TM) with various murine and human cancer cells were 5-8-fold lower than those of control doxorubicin-loaded liposomes, Doxil(TM) or Doxil(TM) modified with a nonspecific IgG. (C) 2007 Elsevier B.V. All rights reserved.