POSTER PRESENTATION Open Access

Combined radiotherapy and immunotherapyusing CPG oligodeoxynucleotides and indolamine2,3 dioxygenase (IDO) blockadeArta M Monjazeb1*, Steven K Grossenbacher2, Gail D Sckisel2, Robert Canter3, Ellen E Sparger4, William Culp4,Michael S Kent4, William J Murphy2

From Society for Immunotherapy of Cancer 28th Annual MeetingNational Harbor, MD, USA. 8-10 November 2013

BackgroundPre-clinical and clinical data demonstrate the effectivenessof combining RT and CpG immunotherapy. There is datato suggest that the effectiveness of CpG immunotherapymay be limited by induction of the immunosuppressiveenzyme, IDO. We test the efficacy and safety of combiningRT and CpG with blockade of the immunosuppressiveenzyme, IDO, using 1-Methyl D-Tryptophan (1-MT).

MethodsTumor bearing mice were treated with RT + IT. IT con-sisted of intratumoral CpG and 1-MT administered in thedrinking water. Tumor growth, survival, toxicity and theimmune profile of various tissues were assessed. Based onpreliminary results a similar clinical trial was initiated at theUC Davis Veterinary Cancer Center testing this approachfor spontaneous metastatic cancers in companion canines.

1Radiation Oncology, UC Davis Health System, Sacramento, CA, USAFull list of author information is available at the end of the article

Figure 1

Monjazeb et al. Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P256http://www.immunotherapyofcancer.org/content/1/S1/P256

© 2013 Monjazeb et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

ResultsIn mice therapy improved overall survival, decreased lungmetastases, decreased mean tumor growth, increasedpercentage of activated dendritic cells in tumor draininglymph nodes, and decreased levels of regulatory T-cells.No treatment related toxicities were observed.In the canine clinical trial 6 patients have been enrolled

to date. No treatment related toxicities have been observed.Preliminary results indicate a robust response at the pri-mary treated disease site but also indicate the induction ofsystemic anti-tumor immunity as demonstrated by regres-sion or stability of un-irradiated metastatic disease. Thetreatment has drastically reduced the level of regulatoryT-cells in the tumor, draining lymph nodes, and peripheralblood in some animals.

ConclusionsCombining RT and IT is more effective than either ther-apy alone. Preliminary results in spontaneous canine can-cers also show promise. Further study is needed todetermine the immunologic mechanism of this therapy.This therapy has limited toxicity in both mice and caninesand is being considered for translation to human studies.

Authors’ details1Radiation Oncology, UC Davis Health System, Sacramento, CA, USA.2Dermatology, UC Davis Health System, Sacramento, CA, USA. 3Surgery, UCDavis Health System, Sacramento, CA, USA. 4Veterinary Medicine, UC DavisHealth System, Davis, CA, USA.

Published: 7 November 2013

doi:10.1186/2051-1426-1-S1-P256Cite this article as: Monjazeb et al.: Combined radiotherapy andimmunotherapy using CPG oligodeoxynucleotides and indolamine 2,3dioxygenase (IDO) blockade. Journal for ImmunoTherapy of Cancer 20131(Suppl 1):P256.

Monjazeb et al. Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P256http://www.immunotherapyofcancer.org/content/1/S1/P256

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