Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD).
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 IC(50) of IL-PLD is 3.1 to 5.4 times lower than that of PLD in CD22+ cell lines while the IC(50) 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.
O'Donnell
Robert T
RT
Division of Hematology and Oncology, Department of Internal Medicine, Davis Cancer Center, University of California, Sacramento, CA, USA.
Martin
Shiloh M
SM
Ma
Yunpeng
Y
Zamboni
William C
WC
Tuscano
Joseph M
JM
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D000922:Immunotoxins; D051918:Sialic Acid Binding Ig-like Lectin 2; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin