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Specific targeting to B cells by lipid-based nanoparticles conjugated with a novel CD22-ScFv

  1. Author:
    Loomis, K.
    Smith, B.
    Feng, Y.
    Garg, H.
    Yavlovich, A.
    Campbell-Massa, R.
    Dimitrov, D. S.
    Blumenthal, R.
    Xiao, X. D.
    Puri, A.

  2. Author Address

    [Loomis, Kristin; Smith, Brandon; Feng, Yang; Garg, Himanshu; Yavlovich, Amichai; Campbell-Massa, Ryan; Dimitrov, Dimiter S.; Blumenthal, Robert; Xiao, Xiaodong; Puri, Anu] NCI, CCR Nanobiol Program, NIH, Frederick, MD 21702 USA.;Puri, A, NCI, CCR Nanobiol Program, NIH, Bldg 469 Rm 216A,POB B,Miller Dr, Frederick, MD 21702 USA.;XiaoX@MedImmune.com apuri@helix.nih.gov
    1. Year: 2010
    2. Date: Apr
    3. Epub Date: 2/4/2010
  2. Journal: Experimental and Molecular Pathology
    1. 88
    2. 2
    3. Pages: 238-249
  4. Type of Article: Article
  5. ISSN: 0014-4800
  1. Abstract:

    The CD22 antigen is a viable target for therapeutic intervention for B-cell lymphomas. Several therapeutic anti-CD22 antibodies as well as an anti-CD22-based immunotoxin (HA22) are currently under investigation in clinical settings. Coupling of anti-CD22 reagents with a nano-drug delivery vehicle is projected to significantly improve treatment efficacies. Therefore, we generated a mutant of the targeting segment of HA22 (a CD22 scFv) to increase its soluble expression (mut-HA22), and conjugated it to the surface of sonicated liposomes to generate immunoliposomes (mut-HA22-liposomes). We examined liposome binding and uptake by CD22(+) B-lymphocytes (BJAB) by using calcein and/or rhodamine PE-labeled liposomes. We also tested the effect of targeting on cellular toxicity with doxorubicin-loaded liposomes. We report that: (i) Binding of mut-HA22-liposomes to BJAB cells was significantly greater than liposomes not conjugated with mut-HA22 (control liposomes), and mut-HA22-liposomes bind to and are taken in by BJAB cells in a dose and temperature-dependent manner, respectively; (ii) This binding occurred via the interaction with the cellular CD22 as pre-incubation of the cells with mut-HA22 blocked subsequent liposome binding; (iii) Intracellular localization of mut-HA22-liposomes at 37 degrees C but not at 4 degrees C indicated that our targeted liposomes were taken up through an energy dependent process via receptor-mediated endocytosis; and (iv) Mut-HA22-liposomes loaded with doxorubicin exhibited at least 2-3 fold more accumulation of doxorubicin in BJAB cells as compared to control liposomes. Moreover, these liposomes showed at least a 2-4 fold enhanced killing of BJAB or Raji cells (CD22(+)), but not SUP-T1 cells (CD22(-)). Taken together these data suggest that these 2nd-generation liposomes may serve as promising carriers for targeted drug delivery to treat patients suffering from B-cell lymphoma. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.yexmp.2010.01.006
  3. PMID: 20122924
  4. PMCID: PMC2849008
  5. View record in Web of Science®
  6. WOS: 000276741000004
  7. NIHMSID: Nihms176649

Library Notes

  1. Fiscal Year: FY2009-2010
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