Novel CD7-specific nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells
Various CD7-targeting immunotoxins have been tested for its potential in treating CD7+ malignant patients but none of those immunotoxins was approved clinically because of lacking enough efficacy and safety. Here we successfully constructed the monovalent and bivalent CD7 nanobody-based immunotoxins PG001 and PG002, both conjugated with a truncated derivative of Pseudomonas exotoxin A respectively. The prokaryotic system expressed immunotoxins not only maintained their binding specificity for CD7-positive cells with a Kd of 16.74 nM and 3.6 nM for PG001 and PG002 respectively, but also efficiently promoted antigen-restricted apoptosis of the CD7-positive leukemia cell lines Jurkat and CEM, and primary T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) cells with an in vitro cytotoxic activity (EC50) in the range of 23-30 pM for PG002. In NOD/SCID mice transplanted with CEM cells, PG001 and PG002 prevented engraftment of the cells and markedly prolonged mouse survival. Owing to the efficient antigen-restricted anti-leukemic activity of PG002, this CD7 nanobody-based immunotoxin exhibited a superior anti-CD7 positive malignancies activity than previously reported immunotoxins, and may represent a promising therapeutic strategy in treating CD7-positive leukemia and lymphoma, which still remain a significant clinical challenge.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Oncotarget - 7(2016), 23 vom: 07. Juni, Seite 34070-83 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tang, Jinle [VerfasserIn] |
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| Links: |
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| Themen: |
Antigens, CD7 |
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| Anmerkungen: |
Date Completed 23.01.2018 Date Revised 13.11.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.18632/oncotarget.8710 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM259445258 |
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| 520 | |a Various CD7-targeting immunotoxins have been tested for its potential in treating CD7+ malignant patients but none of those immunotoxins was approved clinically because of lacking enough efficacy and safety. Here we successfully constructed the monovalent and bivalent CD7 nanobody-based immunotoxins PG001 and PG002, both conjugated with a truncated derivative of Pseudomonas exotoxin A respectively. The prokaryotic system expressed immunotoxins not only maintained their binding specificity for CD7-positive cells with a Kd of 16.74 nM and 3.6 nM for PG001 and PG002 respectively, but also efficiently promoted antigen-restricted apoptosis of the CD7-positive leukemia cell lines Jurkat and CEM, and primary T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) cells with an in vitro cytotoxic activity (EC50) in the range of 23-30 pM for PG002. In NOD/SCID mice transplanted with CEM cells, PG001 and PG002 prevented engraftment of the cells and markedly prolonged mouse survival. Owing to the efficient antigen-restricted anti-leukemic activity of PG002, this CD7 nanobody-based immunotoxin exhibited a superior anti-CD7 positive malignancies activity than previously reported immunotoxins, and may represent a promising therapeutic strategy in treating CD7-positive leukemia and lymphoma, which still remain a significant clinical challenge | ||
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| 700 | 1 | |a Zhu, Xuejun |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Zhenyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xingding |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Zhishu |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Pengjun |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Juhua |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Huimin |e verfasserin |4 aut | |
| 700 | 1 | |a An, Gangli |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Huyong |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Lin |e verfasserin |4 aut | |
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