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

Radiat Res. 2010 Apr;173(4):426-32. doi: 10.1667/RR1904.1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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


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