Selective activation of oxygen-deprived tumor-infiltrating lymphocytes through local intratumoral delivery of CD137 monoclonal antibodies.
Hypoxia-inducing transcription factor-1α (HIF-1α) in hypoxic tumors induces the TNF receptor family member CD137 on tumor-infiltrating lymphocytes. This can be exploited for intratumoral low-dose injection of effective systemic immunotherapy with agonist CD137-specific monoclonal antibodies that induce circulation of systemic tumor-specific effector T cells capable of eradicating distant metastases.
Immune System Activation, Leiden University Medical Center, Leiden, The Netherlands. cmelief@lumc.nl
Cornelis J M
CJ
Melief
D000818:Animals; D005260:Female; D000860:Hypoxia / Q000276:immunology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology*
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9