Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD)

Robert T O'Donnell, Shiloh M. Martin, Yunpeng Ma, William C. Zamboni, Joseph Tuscano

Research output: Contribution to journalArticle

18 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)260-267
Number of pages8
JournalInvestigational New Drugs
Volume28
Issue number3
DOIs
StatePublished - Jun 2010

Keywords

  • CD22
  • Doxorubicin
  • HB22.7
  • Liposomes
  • Non-Hodgkin's lymphoma

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

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