Quantitation of GD2 synthase mRNA by real-time reverse transcription-polymerase chain reaction: Utility in bone marrow purging of neuroblastoma by anti-GD2 antibody 3F8 Journal Article

  

Authors:	Cheung, I. Y.; Lo Piccolo, M. S.; Collins, N.; Kushner, B. H.; Cheung, N. K. V.
Article Title:	Quantitation of GD2 synthase mRNA by real-time reverse transcription-polymerase chain reaction: Utility in bone marrow purging of neuroblastoma by anti-GD2 antibody 3F8
Abstract:	BACKGROUND. Antigen ganglioside GD2 is expressed abundantly on neuroblastoma (NB) cells. Anti-GD2 monoclonal antibody (MoAb) 3F8 kills NB cells by complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Its utility in bone marrow (BM) purging is evaluated by a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay to quantify the mRNA of GD2 synthase, the key enzyme in GD2 synthesis. METHODS. From 1990 to 1993, 10 patients with relapsed/refractory Stage 4 NB participated in a pilot study. In these patients, MoAb 3F8 was used to purge tumor cells from harvested BM that had 5% or less tumor content by immunofluorescence (IF). Subsequently, 31 Stage 4 NB patients who underwent treatment on the N7 protocol (1994-1999) had their BM, which was in remission, purged by 3F8 before 131I-3F8 myeloablative radioimmunotherapy. GD2-positive tumor cells before and after purging were quantified by real-time quantitative RT-PCR of GD2 synthase. RESULTS. GD2 positivity by IF was found before purging in six of eight patients in the pilot study. Five of six patients became negative postpurging. Of 31 patients on the N7 protocol, the more sensitive real-time quantitative RT-PCR detected GD2 synthase mRNA in the BM samples of 7 patients even though the prepurge BM samples were negative by histology and IF. Six of the seven BM samples became negative after 3F8 purging. Marker positivity before purging was statistically significant in predicting overall survival (P = 0.04), but not progression-free survival (P = 0.1). In vitro hematopoietic stem cell recovery and the median time to engraftment were acceptable. CONCLUSION. Tumor cell depletion quantified by real-time RT-PCR demonstrated efficacy of MoAb 3F8 in BM purging. © 2002 American Cancer Society.
Keywords:	clinical article; sensitivity and specificity; bone marrow cells; reverse transcription polymerase chain reaction; hematopoietic stem cell transplantation; monoclonal antibody; fluorescent antibody technique; antibodies, monoclonal; iodine 131; iodine radioisotopes; neuroblastoma; ganglioside gd2; messenger rna; reverse transcriptase polymerase chain reaction; pilot projects; rna, messenger; disease progression; tumor cell; radioimmunotherapy; clonogenic assay; bone marrow neoplasms; autologous bone marrow transplantation; gd2 synthase; synthetase; n-acetylgalactosaminyltransferases; bone marrow purging; humans; human; priority journal; article; purging; quantitative rt-pcr
Journal Title:	Cancer
Volume:	94
Issue:	11
ISSN:	0008-543X
Publisher:	Wiley Blackwell
Date Published:	2002-06-01
Start Page:	3042
End Page:	3048
Language:	English
DOI:	10.1002/cncr.10519
PUBMED:	12115395
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0036604377&partnerID=40&md5=a4550d6b710cd1c568ef76897ad7bb10
Notes:	Export Date: 14 November 2014 -- Source: Scopus

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