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

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

Author information

1
Departments of Pathology, New York University School of Medicine and NYU Cancer Institute and Langone Medical Center, New York, New York 10016, USA. ewnewcomb@gmail.com

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.

PMID:
20334514
PMCID:
PMC3721320
DOI:
10.1667/RR1904.1
[Indexed for MEDLINE]
Free PMC Article

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