- Poster presentation
- Open Access
Combination therapies augment the anti-tumor activity of agonist CD27 mAb in human CD27 transgenic mouse models
© He et al; licensee BioMed Central Ltd. 2013
- Published: 7 November 2013
- Antitumor Activity
- Checkpoint Inhibitor
- Combination Study
- Control Tumor Growth
- Potent Antitumor Activity
CDX-1127 is a fully human antibody to CD27, a TNF receptor superfamily member expressed on the majority of T cells and subsets of NK cells and B cells. We have previously characterized the co-stimulatory activities of CDX-1127 with human T cell cultures and a human CD27 transgenic mouse model (hCD27-Tg). Similar to the findings originally shown by M.J. Glennie and colleagues using an agonist anti-mouse CD27 mAb, CDX-1127 has potent antitumor activity as monotherapy in several syngeneic tumor models in hCD27-Tg mice. In the current studies, we sought to enhance the anti-tumor efficacy of CDX-1127 in challenging tumor settings by combination with clinically relevant therapies. Specifically, we focused on therapies that could decrease or control tumor growth while providing a source of antigen to drive anti-tumor immunity (e.g. chemotherapy or targeted therapy) and immune modifiers that may allow the CD27 driven T cell response to overcome self-regulation (e.g. checkpoint inhibitors or immune activators). In the EG7 delayed treatment model (average tumor size of ~ 50 mm3 when treatment initiated), the combination of CDX-1127 with cyclophosphamide significantly improved survival (>70% survival) compared to either agent alone (<30 % survival). Notably, we found that the combination therapy was associated with increases in the ratio of effector to regulatory T cells in the tumors compared to either single agent group. Additional combination studies with various agents are on-going, and initial studies with CDX-1127 combined with anti-CTLA-4 mAb has shown superior anti-tumor activity (median survival 36.5 days in combination versus 20 days with either single agent). These studies, along with the good safety profile of CDX-1127 reported in a Phase 1 clinical trial, supports the design of future combination studies in patients with cancer.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.