Document Detail


Enhancement of the anti-melanoma response of Hu14.18K322A by αCD40 + CpG.
MedLine Citation:
PMID:  23151945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Targeted monoclonal antibodies (mAb) can be used therapeutically for tumors with identifiable antigens such as disialoganglioside GD2, expressed on neuroblastoma and melanoma tumors. Anti-GD2 mAbs (αGD2) can provide clinical benefit in patients with neuroblastoma. An important mechanism of mAb therapy is antibody-dependent cellular cytotoxicity (ADCC). Combinatorial therapeutic strategies can dramatically increase the anti-tumor response elicited by mAbs. We combined a novel αGD2 mAb, hu14.18K322A, with an immunostimulatory regimen of agonist CD40 mAb and class B CpG-ODN 1826 (CpG). Combination immunotherapy was more effective than the single therapeutic components in a syngeneic model of GD2-expressing B16 melanoma with minimal tumor burden. NK cell depletion in B6 mice showed that NK cells were required for the anti-tumor effect; however, anti-tumor responses were also observed in tumor-bearing SCID/beige mice. Thus, NK cell cytotoxicity did not appear to be essential. Peritoneal macrophages from anti-CD40 + CpG-treated mice inhibited tumor cells in vitro in an hu14.18K322A antibody-dependent manner. These data highlight the importance of myeloid cells as potential effectors in immunotherapy regimens utilizing tumor-specific mAb and suggest that further studies are needed to investigate the therapeutic potential of activated myeloid cells and their interaction with NK cells.
Authors:
Kory L Alderson; Mitchell Luangrath; Megan M Elsenheimer; Stephen D Gillies; Fariba Navid; Alexander L Rakhmilevich; Paul M Sondel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-15
Journal Detail:
Title:  Cancer immunology, immunotherapy : CII     Volume:  62     ISSN:  1432-0851     ISO Abbreviation:  Cancer Immunol. Immunother.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-12     Completed Date:  2013-06-07     Revised Date:  2014-03-20    
Medline Journal Info:
Nlm Unique ID:  8605732     Medline TA:  Cancer Immunol Immunother     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  665-75     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology,  pharmacology*
Antibody-Dependent Cell Cytotoxicity
Antigens, CD40 / agonists,  immunology
Gangliosides / immunology*
Immunization, Passive / methods
Killer Cells, Natural / immunology
Macrophages / immunology
Melanoma, Experimental / immunology*,  therapy*
Mice
Mice, Inbred C57BL
Mice, SCID
Myeloid Cells / immunology
Oligodeoxyribonucleotides / immunology,  pharmacology*
Grant Support
ID/Acronym/Agency:
CA032685/CA/NCI NIH HHS; CA14520/CA/NCI NIH HHS; CA166105/CA/NCI NIH HHS; CA87025/CA/NCI NIH HHS; F31 GM067386/GM/NIGMS NIH HHS; GM067386/GM/NIGMS NIH HHS; P30 CA014520/CA/NCI NIH HHS; R01 CA032685/CA/NCI NIH HHS; R01 CA087025/CA/NCI NIH HHS; R01 CA166105/CA/NCI NIH HHS; UL1 TR000427/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD40; 0/CpG ODN 1826; 0/Gangliosides; 0/Oligodeoxyribonucleotides; 65988-71-8/ganglioside, GD2
Comments/Corrections

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