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Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab.
J. Hematol. Oncol. 8:111 (2015)
The bispecific T cell engager blinatumomab has shown encouraging clinical activity in B-precursor acute lymphoblastic leukemia (ALL). However, about half of relapsed/refractory patients do not respond to therapy. Here, we present the case of a 32-year-old male patient with refractory B-precursor ALL who was resistant to treatment with blinatumomab. Bone marrow immunohistochemistry revealed T cell infiltrates and an increase in programmed death-ligand 1 (PD-L1)-positive ALL cells as a potential immune escape mechanism. We were able to recapitulate the clinical observation in vitro by showing that blinatumomab was not able to mediate cytotoxicity of CD19-positive ALL cells using autologous T cells. In contrast, the addition of healthy donor T cells led to lysis of ALL cells. These results strongly encourage further systematic evaluation of checkpoint molecules in cases of blinatumomab treatment failure and might highlight a possible mechanism to overcome resistance to this otherwise highly effective treatment.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
All ; Blinatumomab ; Combination Therapy ; Immune Checkpoints ; Immunotherapy ; T Cells
e-ISSN
1756-8722
Journal
Journal of Hematology & Oncology
Quellenangaben
Volume: 8,
Article Number: 111
Publisher
BioMed Central
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CCG Hematopoetic Cell Transplants (IMI-KHZ)