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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2014

Open Access 01-12-2014 | Research

Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine

Authors: Anna R Kwilas, Andressa Ardiani, Renee N Donahue, Dana T Aftab, James W Hodge

Published in: Journal of Translational Medicine | Issue 1/2014

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Abstract

Background

Growing awareness of the complexity of carcinogenesis has made multimodal therapies for cancer increasingly compelling and relevant. In recent years, immunotherapy has gained acceptance as an active therapeutic approach to cancer treatment, even though cancer is widely considered an immunosuppressive disease. Combining immunotherapy with targeted agents that have immunomodulatory capabilities could significantly improve its efficacy.

Methods

We evaluated the ability of cabozantinib, a receptor tyrosine kinase inhibitor, to modulate the immune system in vivo as well as alter the phenotype of tumor cells in vitro in order to determine if this inhibitor could act synergistically with a cancer vaccine.

Results

Our studies indicated that cabozantinib altered the phenotype of MC38-CEA murine tumor cells, rendering them more sensitive to immune-mediated killing. Cabozantinib also altered the frequency of immune sub-populations in the periphery as well as in the tumor microenvironment, which generated a more permissive immune environment. When cabozantinib was combined with a poxviral-based cancer vaccine targeting a self-antigen, the combination significantly reduced the function of regulatory T cells and increased cytokine production from effector T cells in response to the antigen. These alterations to the immune landscape, along with direct modification of tumor cells, led to markedly improved antitumor efficacy.

Conclusions

These studies support the clinical combination of cabozantinib with immunotherapy for the treatment of cancer.
Appendix
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Metadata
Title
Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine
Authors
Anna R Kwilas
Andressa Ardiani
Renee N Donahue
Dana T Aftab
James W Hodge
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2014
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-014-0294-y

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