Justin Patrick Hart MD, PhD, Presenter: Nothing to Disclose

Jay Carpenter, Abstract Co-Author: Nothing to Disclose

Nalini Patel, Abstract Co-Author: Nothing to Disclose

David Valdecanas, Abstract Co-Author: Nothing to Disclose

Kathryn Ann Mason, Abstract Co-Author: Researcher, Agenix Limited Researcher, American BioSciences, Inc Researcher, Amgen Inc Researcher, Coley Pharmaceutical Group, Inc Researcher, ImClone Systems Incorporated Researcher, Inotek Pharmaceuticals Corporation Researcher, Merck & Co, Inc Researcher, Otsuka Pharmaceutical Co, Ltd Researcher, Pfizer, Inc Royalties, Pfizer Inc

Luka Milas MD, PhD, Abstract Co-Author: Researcher, Amgen Inc Researcher, ImClone Systems Incorporated Researcher, Inotek Pharmaceuticals Corporation Researcher, Pfizer Inc

Our earlier studies (Milas L, Cancer Res. 5074 (2004)) showed that CpG ODN, a Toll-like receptor 9-mediated immunomodulator, enhances both tumor growth delay and tumor cure when combined with radiotherapy (XRT). This study was conducted to determine the mechanisms involved in the enhanced local tumor control and whether the combination therapy induces systemic anti-tumor rejection.

FSa sarcomas were generated in both hind thighs, treatment was restricted to right-sided tumors. At 8mm tumors received 20 Gy.  CpG ODN 1826 was injected peritumorally at 6 mm, 8 mm and 4 days later. Controls included treatments with XRT only, CpG ODN only, and no treatment. At days 4 and 8 groups of mice were killed and draining lymph nodes (DLN) were collected and analyzed with flow cytometry.

CpG ODN 1826 alone exerted anti-tumor actions as assessed 18 days after tumors measured 6mm. It reduced the size of treated tumors from 14.9 ±0.3 (SEM) mm to 9.7 ±0.7 mm and untreated, left tumor size decreased from 14.1 ±0.4 mm to 9.0 ±1.0 mm. XRT alone reduced tumor size to 9.2 ±0.6 mm, but did not affect the unirradiated, left tumor. In mice receiving both CpG ODN & XRT, the treated tumors were reduced to 6.8 ±0.4 mm while the untreated tumors measured 7.6 ±0.6 mm.  Analysis of DLN demonstrated increased CD8+ and CD11c+ cells 4 days after tumors measured 8mm in animals receiving CpG ODN and CpG ODN & XRT compared to XRT alone. 8 days after tumors measured 8mm, increased CD11c+ cells were observed in DLN of animals treated with CpG ODN & XRT as compared to animals treated with XRT alone.  

Our results demonstrated that combining CpG ODN 1826 with radiotherapy improves local tumor control in part by significantly altering systemic immune response. Increased numbers of CD11c+ and CD8+ cells were found within tumor DLN following treatment in animals receiving CpG ODN & XRT as compared to animals receiving XRT alone. The enhanced tumor control observed following treatment with CpG ODN & XRT may be due to increased numbers of cytolytic T cells. Treatment with CpG ODN induced measurable tumor control at distant sites of disease.

A systemic anti-tumor immune response capable of eliminating metastatic disease may be inducible when an immune stimulator such as CpG ODN is administered in conjunction with tumor irradiation.

Hart, J, Carpenter, J, Patel, N, Valdecanas, D, Mason, K, Milas, L, CpG Oligodeoxynucleotides (CpG ODN) Immunotherapy Enhances Tumor Radioresponse: Systemic Effects and Mechanisms.  Radiological Society of North America 2008 Scientific Assembly and Annual Meeting, February 18 - February 20, 2008 ,Chicago IL. http://archive.rsna.org/2008/6012476.html