Journal article
Enhancement of the anti-melanoma response of Hu14.18K322A by αCD40 + CpG
Cancer Immunology, Immunotherapy, Vol.62(4), pp.665-675
2013
DOI: 10.1007/s00262-012-1372-8
PMCID: PMC3578100
PMID: 23151945
Abstract
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.
Details
- Title: Subtitle
- Enhancement of the anti-melanoma response of Hu14.18K322A by αCD40 + CpG
- Creators
- Kory L. Alderson - University of Wisconsin–MadisonMitchell Luangrath - University of Wisconsin–MadisonMegan M. Elsenheimer - University of Wisconsin–MadisonStephen D. Gillies - scPharmaceuticalsFariba Navid - St. Jude Children's Research HospitalAlexander L. Rakhmilevich - University of Wisconsin Carbone Cancer CenterPaul M. Sondel - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cancer Immunology, Immunotherapy, Vol.62(4), pp.665-675
- Publisher
- Springer-Verlag
- DOI
- 10.1007/s00262-012-1372-8
- PMID
- 23151945
- PMCID
- PMC3578100
- ISSN
- 0340-7004
- eISSN
- 1432-0851
- Language
- English
- Date published
- 2013
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics
- Record Identifier
- 9984353834802771
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