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 Citations (Scopus)

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

Fingerprint

liposomal doxorubicin
1-dodecylpyridoxal
Non-Hodgkin's Lymphoma
Doxorubicin
Cell Line
Inhibitory Concentration 50
Fluorescent Antibody Technique
Cause of Death
Monoclonal Antibodies
Staining and Labeling
Recurrence
Drug Therapy
Neoplasms
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD). / O'Donnell, Robert T; Martin, Shiloh M.; Ma, Yunpeng; Zamboni, William C.; Tuscano, Joseph.

In: Investigational New Drugs, Vol. 28, No. 3, 06.2010, p. 260-267.

Research output: Contribution to journalArticle

O'Donnell, Robert T ; Martin, Shiloh M. ; Ma, Yunpeng ; Zamboni, William C. ; Tuscano, Joseph. / Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD). In: Investigational New Drugs. 2010 ; Vol. 28, No. 3. pp. 260-267.
@article{e17114b96edd494a82cd0618caae7f1f,
title = "Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD)",
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.",
keywords = "CD22, Doxorubicin, HB22.7, Liposomes, Non-Hodgkin's lymphoma",
author = "O'Donnell, {Robert T} and Martin, {Shiloh M.} and Yunpeng Ma and Zamboni, {William C.} and Joseph Tuscano",
year = "2010",
month = "6",
doi = "10.1007/s10637-009-9243-7",
language = "English (US)",
volume = "28",
pages = "260--267",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "3",

}

TY - JOUR

T1 - Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD)

AU - O'Donnell, Robert T

AU - Martin, Shiloh M.

AU - Ma, Yunpeng

AU - Zamboni, William C.

AU - Tuscano, Joseph

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

KW - CD22

KW - Doxorubicin

KW - HB22.7

KW - Liposomes

KW - Non-Hodgkin's lymphoma

UR - http://www.scopus.com/inward/record.url?scp=77952241780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952241780&partnerID=8YFLogxK

U2 - 10.1007/s10637-009-9243-7

DO - 10.1007/s10637-009-9243-7

M3 - Article

C2 - 19306119

AN - SCOPUS:77952241780

VL - 28

SP - 260

EP - 267

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 3

ER -