Targeting pediatric leukemia-propagating cells with anti-CD200 antibody therapy
| Autor: | Allison Blair, John Moppett, Benjamin C Ede, Paraskevi Diamanti, Robert A. Uger, Charlotte V. Cox |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Neoplasm
Residual medicine.drug_class CD58 Antigens CD19 CD34 Monoclonal antibody CD19 Mice Immune system In vivo Precursor B-Cell Lymphoblastic Leukemia-Lymphoma hemic and lymphatic diseases medicine Animals Humans Child Lymphoid Neoplasia biology business.industry Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Flow Cytometry medicine.disease Chimeric antigen receptor Leukemia Cancer research biology.protein business |
| Zdroj: | Blood Adv Diamanti, P, Cox, C V, Blair, A, Ede, B & Moppett, J P 2021, ' Targeting pediatric leukemia propagating cells using anti-CD200 antibody therapy. ', Blood Advances, vol. 5, no. 18, pp. 3694–3708 . https://doi.org/10.1182/bloodadvances.2020003534 |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | Treating refractory pediatric acute lymphoblastic leukemia (ALL) remains a challenge despite impressive remission rates (>90%) achieved in the last decade. The use of innovative immunotherapeutic approaches such as anti-CD19 chimeric antigen receptor T cells does not ensure durable remissions, because leukemia-propagating cells (LPCs) that lack expression of CD19 can cause relapse, which signifies the need to identify new markers of ALL. Here we investigated expression of CD58, CD97, and CD200, which were previously shown to be overexpressed in B-cell precursor ALL (BCP-ALL) in CD34+/CD19+, CD34+/CD19–, CD34–/CD19+, and CD34–/CD19– LPCs, to assess their potential as therapeutic targets. Whole-genome microarray and flow cytometric analyses showed significant overexpression of these molecules compared with normal controls. CD58 and CD97 were mainly co-expressed with CD19 and were not a prerequisite for leukemia engraftment in immune deficient mice. In contrast, expression of CD200 was essential for engraftment and serial transplantation of cells in measurable residual disease (MRD) low-risk patients. Moreover, these CD200+ LPCs could be targeted by using the monoclonal antibody TTI-CD200 in vitro and in vivo. Treating mice with established disease significantly reduced disease burden and extended survival. These findings demonstrate that CD200 could be an attractive target for treating low-risk ALL, with minimal off-tumor effects that beset current immunotherapeutic approaches. |
| Databáze: | OpenAIRE |
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