Radiotherapy enhances antitumor effect of anti-CD137 therapy in a mouse Glioma model.

Abstract

Previously, we reported that peripheral vaccination of mice with modified autologous tumor cells secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with ionizing radiation to the whole brain cured 50% of mice using a syngeneic, intracranial model of murine high-grade glioma. Here, we tested the combination of radiotherapy (4 Gy x 2) with an immunotherapeutic approach using an anti-CD137 antibody directed to the co-stimulatory molecule CD137. The CD137 antibody has shown promise in generating effective antitumor responses in several animal models and has demonstrated a favorable toxicity profile in the clinic. The combination of radiation and anti-CD137 therapy resulted in complete tumor eradication and prolonged survival in six of nine (67%) mice with established brain tumors (P = 0.0009). Five of six (83%) long-term survivors in the combination group demonstrated antitumor immunity by rejecting challenge tumors. Antitumor immunity was associated with an increased number of tumor-infiltrating lymphocytes (TILs) in brain tumors and increased tumor-specific production of gammaIFN. In view of the finding that radiation enhanced the antitumor effect of anti-CD137 therapy, this approach should be studied further for clinical translation.

• Authors: Elizabeth W Newcomb, Yevgeniy Lukyanov, Noriko Kawashima, Michelle Alonso-Basanta, Shu-Chi Wang, Mengling Liu, Maria Jure-Kunkel, David Zagzag, Sandra Demaria, Silvia C Formenti
• Journal: Radiation research (Radiat Res) Vol. 173 Issue 4 Pg. 426-32 (Apr 2010) ISSN: 1938-5404 [Electronic] United States
• PMID: 20334514 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Tumor Necrosis Factor Receptor Superfamily, Member 9

Topics

• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• Antineoplastic Agents (immunology, therapeutic use)
• Brain Neoplasms (immunology, therapy)
• Cell Line, Tumor
• Disease Models, Animal
• Female
• Glioma (immunology, therapy)
• Humans
• Mice
• Mice, Inbred C57BL
• Radiotherapy, Adjuvant
• Survival Analysis
• Survival Rate
• Treatment Outcome
• Tumor Necrosis Factor Receptor Superfamily, Member 9 (antagonists & inhibitors, immunology)