Examination of CD302 as a potential therapeutic target for acute myeloid leukemia

Tsun Ho Lo, Edward Abadir, Robin E. Gasiorowski, Karieshma Kabani, Murari Ramesh, Daniel Orellana, Phillip D. Fromm, Fiona Kupresanin, Elizabeth Newman, Ilona Cunningham, Derek N. J. Hart, Pablo A. Silveira, Georgina J. Clark*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)
9 Downloads (Pure)

Abstract

Acute myeloid leukemia (AML) is the most common form of adult acute leukemia with ~20,000 new cases yearly. The disease develops in people of all ages, but is more prominent in the elderly, who due to limited treatment options, have poor overall survival rates. Monoclonal antibodies (mAb) targeting specific cell surface molecules have proven to be safe and effective in different haematological malignancies. However, AML target molecules are currently limited so discovery of new targets would be highly beneficial to patients. We examined the C-type lectin receptor CD302 as a potential therapeutic target for AML due to its selective expression in myeloid immune populations. In a cohort of 33 AML patients with varied morphological and karyotypic classifications, 88% were found to express CD302 on the surface of blasts and 80% on the surface of CD34+ CD38- population enriched with leukemic stem cells. A mAb targeting human CD302 was effective in mediating antibody dependent cell cytotoxicity and was internalised, making it amenable to toxin conjugation. Targeting CD302 with antibody limited in vivo engraftment of the leukemic cell line HL-60 in NOD/SCID mice. While CD302 was expressed in a hepatic cell line, HepG2, this molecule was not detected on the surface of HepG2, nor could HepG2 be killed using a CD302 antibody-drug conjugate. Expression was however found on the surface of haematopoietic stem cells suggesting that targeting CD302 would be most effective prior to haematopoietic transplantation. These studies provide the foundation for examining CD302 as a potential therapeutic target for AML.

Original languageEnglish
Article numbere0216368
Pages (from-to)1-15
Number of pages15
JournalPLoS ONE
Volume14
Issue number5
DOIs
Publication statusPublished - 10 May 2019
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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