Purine Nucleoside Phosphorylase Inhibitors as Novel Immuno-Oncology Agent and Vaccine Adjuvant

Purine Nucleoside Phosphorylase (PNP) deficiency in humans causes lymphopenia and this provided the rationale for developing PNP inhibitors as immunosuppressive agents. However, carefulre-evaluation of clinical history of PNP deficient patients and clinical experience with PNP inhibitors together with new experimental data suggest inhibition of PNP may have immune activating effects through elevation of guanosine and activation of various toll-like receptors (TLRs). This paper proposes a mechanism of action for the immune activating effects of PNP inhibition.