2. Academic Validation
  3. Effects of CD49d-targeted antisense-oligonucleotide on α4 integrin expression and function of acute lymphoblastic leukemia cells: Results of in vitro and in vivo studies

Effects of CD49d-targeted antisense-oligonucleotide on α4 integrin expression and function of acute lymphoblastic leukemia cells: Results of in vitro and in vivo studies

  • PLoS One. 2017 Nov 8;12(11):e0187684. doi: 10.1371/journal.pone.0187684.
Yann Duchartre 1,  Stefanie Bachl 1 2,  Hye Na Kim 1,  Eun Ji Gang 1,  Solah Lee 1,  Hsiao-Chuan Liu 3,  Kirk Shung 3,  Ruth Xu 1,  Aaron Kruse 1 4,  George Tachas 5,  Halvard Bonig 2 6,  Yong-Mi Kim 1
Affiliations

Affiliations

  • 1 Department of Pediatrics, Division of Hematology and Oncology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, United States of America.
  • 2 Institute for Transfusion Medicine and Immunohematology, Goethe University, and German Red Cross Blood Service Baden-Württemberg-Hessen, Frankfurt, Germany.
  • 3 Department of Biomedical Engineering, University of Southern California, Los Angeles, United States of America.
  • 4 Department of Pathology, University of Southern California, Los Angeles, United States of America.
  • 5 Antisense Therapeutics Limited, Toorak, Victoria, Australia.
  • 6 Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, United States of America.
PMID: 29117236 DOI: 10.1371/journal.pone.0187684
Abstract

We recently demonstrated the effectiveness of blocking CD49d with anti-functional Antibodies or small molecule inhibitors as a rational targeted approach to the treatment of acute leukemia in combination with chemotherapy. Antisense oligonucleotide promises to be no less specific than Antibodies and inhibitors, but more interesting for pharmacokinetics and pharmacodynamics. We addressed this using the published CD49d antisense drug ATL1102. In vitro, we incubated/nucleofected the ALL cell line Kasumi-2 with ATL1102. In vivo, immunodeficient hosts were engrafted with primary ALL cells and treated with ATL1102. Changes in expression of CD49d mRNA and CD49d protein, and of cooperating gene products, including ß1 Integrin and CXCR4, as well as survival in the mouse experiments were quantified. We observed dose-dependent down-regulation of CD49d mRNA and protein levels and its partner Integrin ß1 cell surface protein level and, up-regulation of CXCR4 surface expression. The suppression was more pronounced after nucleofection than after incubation, where down-regulation was significant only at the higher doses. In vivo effects of ATL1102 were not sufficient to translate into "clinical" benefit in the leukemia model. In summary, Antisense Oligonucleotides are successful tools for specifically modulating gene expression but sufficient delivery to down-regulate CD49d in vivo may be difficult to achieve.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z