Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD) |
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| Authors: | Robert T O’Donnell Shiloh M Martin Yunpeng Ma William C Zamboni |
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| Institution: | (1) Division of Hematology and Oncology, Department of Internal Medicine, Davis Cancer Center, University of California, Sacramento, CA, USA;(2) Northern California Veterans Administration Healthcare System, Mather, CA, USA;(3) Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA;(4) Molecular Therapeutics Program, UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA;(5) UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA;(6) Carolina Center of Cancer Nanotechnology Excellence, University of North Carolina, Chapel Hill, NC, USA;(7) UC Davis Cancer Center, Division of Hematology and Oncology, 4501 X Street, Suite 3016, Sacramento, CA 95817, USA; |
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| Abstract: | Non-Hodgkin’s lymphoma (NHL) is the sixth most common cause of cancer deaths in the U.S. Most NHLs initially respond well
to chemotherapy, but relapse is common and treatment is often limited due to the toxicity of chemotherapeutic agents. Pegylated-liposomal
doxorubicin (PLD, Ben Venue Laboratories, Inc), a produces less myelotoxicity than non-liposomal (NL) doxorubicin. To further
enhance efficacy and NHL targeting and to decrease toxicity, we conjugated an anti-CD22 monoclonal antibody (HB22.7) to the
surface of PLD, thereby creating CD22-targeted immunoliposomal PLD (IL-PLD). HB22.7 was successfully conjugated to PLD and
the resulting IL-PLD exhibits specific binding to CD22-expressing cells as assessed by immunofluorescence staining. IL-PLD
exhibits more cytotoxicity than PLD in CD22 positive cell lines but does not increase killing of CD22 negative cells. The
IC50 of IL-PLD is 3.1 to 5.4 times lower than that of PLD in CD22+ cell lines while the IC50 of IL-PLD is equal to that of PLD in CD22- cells. Furthermore, IL-PLD remained bound to the CD22+ cells after washing and
continued to exert cytotoxic effects, while PLD and NL- doxorubicin could easily be washed from these cells. |
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