Combined anti-CD40 and anti-IL-23 monoclonal antibody therapy effectively suppresses tumor growth and metastases

Von Scheidt, Bianca, Leung, Patrick S.K., Yong, Michelle C.R., Zhang, Yu, Towne, Jennifer E., Smyth, Mark J. and Teng, Michele W.L. (2014) Combined anti-CD40 and anti-IL-23 monoclonal antibody therapy effectively suppresses tumor growth and metastases. Cancer Research, 74 9: 2412-2421. doi:10.1158/0008-5472.CAN-13-1646


Author Von Scheidt, Bianca
Leung, Patrick S.K.
Yong, Michelle C.R.
Zhang, Yu
Towne, Jennifer E.
Smyth, Mark J.
Teng, Michele W.L.
Title Combined anti-CD40 and anti-IL-23 monoclonal antibody therapy effectively suppresses tumor growth and metastases
Journal name Cancer Research   Check publisher's open access policy
ISSN 1538-7445
0008-5472
Publication date 2014-05-01
Year available 2014
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-13-1646
Volume 74
Issue 9
Start page 2412
End page 2421
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Formatted abstract
Tumor-induced immunosuppression remains one of the major obstacles to many potentially effective cancer therapies and vaccines. Host interleukin (IL)-23 suppresses the immune response during tumor initiation, growth, and metastases, and neutralization of IL-23 causes IL-12–dependent antitumor effects. Here, we report that combining agonistic anti-CD40 monoclonal antibodies (mAb) to drive IL-12 production and anti–IL-23 mAbs to counter the tumor promoting effects of IL-23 has greater antitumor activity than either agent alone. This increased antitumor efficacy was observed in several experimental and spontaneous lung metastases models as well as in models of de novo carcinogenesis. The combination effects were dependent on host IL-12, perforin, IFN-γ, natural killer, and/or T cells and independent of host B cells and IFN-αβ sensitivity. Interestingly, in the experimental lung metastases tumor models, we observed that intracellular IL-23 production was specifically restricted to MHC-IIhiCD11c+CD11b+ cells. Furthermore, an increase in proportion of these IL-23–producing cells was detected only in tumor models where IL-23 neutralization was therapeutic. Overall, these data suggest the clinical potential of using anti-CD40 (push) and anti–IL-23 mAbs (pull) to tip the IL-12/23 balance in established tumors.
Keyword CD40 ligand monoclonal antibody
Interleukin 23 antibody
Cancer inhibition
Metastasis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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