Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Journal of hematology & oncology - 8(2015) vom: 08. Okt., Seite 111 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Köhnke, Thomas [VerfasserIn] |
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| Links: |
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| Themen: |
4FR53SIF3A |
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| Anmerkungen: |
Date Completed 11.07.2016 Date Revised 10.03.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s13045-015-0213-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM253515211 |
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| 245 | 1 | 0 | |a Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab |
| 264 | 1 | |c 2015 | |
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| 500 | |a Date Completed 11.07.2016 | ||
| 500 | |a Date Revised 10.03.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Antigens, CD19 |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a CD274 protein, human |2 NLM | |
| 650 | 7 | |a CD3 Complex |2 NLM | |
| 650 | 7 | |a PDCD1 protein, human |2 NLM | |
| 650 | 7 | |a Programmed Cell Death 1 Receptor |2 NLM | |
| 650 | 7 | |a blinatumomab |2 NLM | |
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| 700 | 1 | |a Krupka, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Tischer, Johanna |e verfasserin |4 aut | |
| 700 | 1 | |a Knösel, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Subklewe, Marion |e verfasserin |4 aut | |
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