In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 13, No. 18 ( 2007-09-15), p. 5613s-5620s
Abstract:
Purpose: We previously generated a mouse monoclonal antibody (mAb) specific for the tumor-associated GD2 ganglioside antigen. Here, we describe the development of a chimeric anti-GD2 mAb for more effective tumor immunotherapy. Experimental Design: We cloned the cDNA encoding the immunoglobulin light and heavy chains of the 60C3 anti-GD2 mAb, and constructed chimeric genes by linking the cDNA fragments of the variable regions of the murine light and heavy chains to cDNA fragments of the human κ and γ1 constant regions, respectively. Results: The resultant chimeric anti-GD2 mAb, c.60C3, showed identical binding affinity and specificity to that of its murine counterpart. Both c.60C3 and 60C3 were rapidly internalized by tumor cells at 37°C. When human serum and human natural killer cells were used as effectors in complement-mediated cytotoxicity and antibody-dependent cell cytotoxicity, respectively, c.60C3 was more effective in killing GD2-expressing tumor cells. However, c.60C3 was ineffective at inducing cell death by apoptosis, although binding of 60C3 induced apoptotic death in vitro. In an in vivo, GD2-expressing, syngeneic tumor model, i.v. injection of c.60C3, but not of 60C3, significantly suppressed tumor growth in mice (P & lt; 0.0005). Conclusion: Immune effector functions mediated by this antibody and its potentially reduced immunogenicity make chimeric c.60C3 a promising therapeutic agent against neuroectodermic tumors.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-07-1057
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2007
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
