Targeted killing of the Nalm-6 cells with 2E8-Genistein immunotoxin and its mechanism

OBJECTIVE: Leukemia is the most common hematopoietic malignancies in children. Chemotherapy is currently the primary modality of treatment for this fatal disease. Although chemotherapy is very effective in terms of cell killing, severe side effects such as severe infections, intracranial hemorrhage...

Description complète

Détails bibliographiques
Publié dans:Zhonghua er ke za zhi = Chinese journal of pediatrics. - 1960. - 47(2009), 1 vom: 03. Jan., Seite 57-61
Auteur principal: Chen, Ying-hu (Auteur)
Autres auteurs: Tang, Yong-min, Shen, Hong-qiang, Song, Hua, Yang, Shi-long, Shi, Shu-wen, Qian, Bai-qin, Xu, Wei-qun, Ning, Bo-tao
Format: Article
Langue:Chinese
Publié: 2009
Accès à la collection:Zhonghua er ke za zhi = Chinese journal of pediatrics
Sujets:English Abstract Journal Article Research Support, Non-U.S. Gov't Antibodies, Monoclonal Antigens, CD19 Immunotoxins Genistein DH2M523P0H
LEADER 01000caa a22002652c 4500
001 NLM189726210
003 DE-627
005 20250210134726.0
007 tu
008 231223s2009 xx ||||| 00| ||chi c
028 5 2 |a pubmed25n0632.xml 
035 |a (DE-627)NLM189726210 
035 |a (NLM)19573385 
040 |a DE-627  |b ger  |c DE-627  |e rakwb 
041 |a chi 
100 1 |a Chen, Ying-hu  |e verfasserin  |4 aut 
245 1 0 |a Targeted killing of the Nalm-6 cells with 2E8-Genistein immunotoxin and its mechanism 
264 1 |c 2009 
336 |a Text  |b txt  |2 rdacontent 
337 |a ohne Hilfsmittel zu benutzen  |b n  |2 rdamedia 
338 |a Band  |b nc  |2 rdacarrier 
500 |a Date Completed 11.01.2011 
500 |a Date Revised 07.06.2016 
500 |a published: Print 
500 |a Citation Status MEDLINE 
520 |a OBJECTIVE: Leukemia is the most common hematopoietic malignancies in children. Chemotherapy is currently the primary modality of treatment for this fatal disease. Although chemotherapy is very effective in terms of cell killing, severe side effects such as severe infections, intracranial hemorrhage etc. are frequently encountered due to its poor selective damage between normal and malignant cells or tissues. Thus, a new therapy with highly selective killing of malignant cells which leaves the normal cells unaffected is desperately desired. The aim of this study was to investigate the targeting efficacy in vitro with a new clone of anti-human CD19 antibody immunotoxin 2E8-Genistein on B lineage leukemia cell line Nalm-6 cells and its mechanisms in order to provide the evidence of target therapy on B lineage leukemia and lymphoma 
520 |a METHODS: 2E8-Genistein immunotoxin was generated by conjugating Mab 2E8 with a tyrosine kinase inhibitor, Genistein (Gen) via the Sulfo-SANPAH, an ultra-violet sensitive reagent. Nalm-6, a CD19+ B cell leukemia cell line, was used as target cells, while Molt-3, a CD19-T cell leukemia cell line, was taken as the negative control. The morphology of the cells was observed under the reverted reversed light microscope and the viability was checked with either trypan blue exclusion or MTT methods. Two-color flow cytometry was applied to study the mechanism of cell killing 
520 |a RESULTS: After 24 hours of culture, 2E8-Genistein showed marked target killing on Nalm-6 cells at nine different concentrations from 20 nmol/L through 100 nmol/L with cell survival rates from (71.8 +/- 7.9)% down to (16.6 +/- 12.9)%, respectively (n = 3), which were all significantly lower than that of control group (100 +/- 13.9)% (P < 0.05). The killing effect was even more significant when the concentration was over 80 nmol/L. The growth inhibition rates of this immunotoxin on Nalm-6 cells were 82%, 84% and 94%, respectively at 24, 48 and 72 hours of culture in a time dependent manner. Significant difference was observed between the cell growth curve of Nalm-6 cultured with 100 nmol/L of 2E8-Gen and those of Nalm-6 cultured with medium (blank), PBS (negative control) or the same concentration of pure 2E8 antibody (negative control) groups (F = 152.15, P = 2.15 x 10(-7)), but there was no significant difference among the three control groups (F = 1.51, P = 0.29). When Molt-3 cells were used as target cells, the cell growth curves of Molt-3 cultured with 2E8-Gen (100 nmol/L) and with negative control of blank did not show any significant difference (F = 0.34, P = 0.59). PI/FITC Annexin V double staining analysis with flow cytometry showed that the positive rate (33.45 +/- 8.77)% of early apoptosis on Nalm-6 cells induced by 100 nmol/L of 2E8-Genistein was significantly higher than that of negative control of blank (10.44% +/- 1.28%, t = -4.39, P = 0.001) at 24 hours of culture 
520 |a CONCLUSION: 2E8-Genistein immunotoxin can significantly target the Nalm-6 cells in vitro in a time response manner and the apoptosis induction is involved in the course of this killing effect 
650 4 |a English Abstract 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a Antibodies, Monoclonal  |2 NLM 
650 7 |a Antigens, CD19  |2 NLM 
650 7 |a Immunotoxins  |2 NLM 
650 7 |a Genistein  |2 NLM 
650 7 |a DH2M523P0H  |2 NLM 
700 1 |a Tang, Yong-min  |e verfasserin  |4 aut 
700 1 |a Shen, Hong-qiang  |e verfasserin  |4 aut 
700 1 |a Song, Hua  |e verfasserin  |4 aut 
700 1 |a Yang, Shi-long  |e verfasserin  |4 aut 
700 1 |a Shi, Shu-wen  |e verfasserin  |4 aut 
700 1 |a Qian, Bai-qin  |e verfasserin  |4 aut 
700 1 |a Xu, Wei-qun  |e verfasserin  |4 aut 
700 1 |a Ning, Bo-tao  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Zhonghua er ke za zhi = Chinese journal of pediatrics  |d 1960  |g 47(2009), 1 vom: 03. Jan., Seite 57-61  |w (DE-627)NLM136249191  |x 0578-1310  |7 nnas 
773 1 8 |g volume:47  |g year:2009  |g number:1  |g day:03  |g month:01  |g pages:57-61 
912 |a GBV_USEFLAG_A 
912 |a SYSFLAG_A 
912 |a GBV_NLM 
912 |a GBV_ILN_11 
912 |a GBV_ILN_20 
912 |a GBV_ILN_22 
912 |a GBV_ILN_24 
912 |a GBV_ILN_31 
912 |a GBV_ILN_39 
912 |a GBV_ILN_40 
912 |a GBV_ILN_50 
912 |a GBV_ILN_61 
912 |a GBV_ILN_65 
912 |a GBV_ILN_69 
912 |a GBV_ILN_70 
912 |a GBV_ILN_72 
912 |a GBV_ILN_120 
912 |a GBV_ILN_130 
912 |a GBV_ILN_227 
912 |a GBV_ILN_244 
912 |a GBV_ILN_285 
912 |a GBV_ILN_294 
912 |a GBV_ILN_350 
912 |a GBV_ILN_665 
912 |a GBV_ILN_813 
951 |a AR 
952 |d 47  |j 2009  |e 1  |b 03  |c 01  |h 57-61