Pegarginase(Bio-Cancer Treatment International Ltd.)

Research findings evermore suggest a crucial role of myeloid-derived suppressor cells (MDSCs) in chronic lung diseases including asthma. Previously, we showed that intravenous (IV) treatment with a prostaglandin E2 receptor 4 (EP4) agonist, L-902,688, promoted MDSC suppressive activity. IV therapy with L-902,688 and BCT-100, a human pegylated arginase-1, ameliorated lung inflammatory features in a murine model of asthma. Here, we further investigate the potential therapeutic approach by studying the local therapy effects on the lungs after intranasal (IN) application. Using a two-week model of house dust mite (HDM)-induced murine asthma, the effect of IN treatment with L-902,688 or BCT-100 on in vivo lung function, inflammatory features of asthma and MDSC generation and activation was studied. Our experiments demonstrated increased suppressive activity of pulmonary MDSCs after induction of allergic airway disease. IN treatment with L-902,688 and BCT-100 further enhanced the immunosuppressive activity of pulmonary MDSCs. Additionally, treatment with BCT-100 reduced pulmonary T cell numbers. Asthmatic mice that received IN L-902,688 showed improved in vivo lung function. In conclusion, our results underline the potential of modulating MDSCs systemically or locally as a future therapeutic option in airway inflammatory diseases such as asthma.

The survival of acute myeloid leukaemia (AML) patients aged over 60 has been suboptimal historically, whether they are treated using hypomethylating agents, low‐dose cytarabine (LDAC) or venetoclax‐based regimens. Progress is being made, however, for subgroups with favourable molecular or cytogenetic findings. Arginine metabolism plays a key role in AML pathophysiology. We report the only randomised study of LDAC with recombinant arginase BCT‐100 versus LDAC alone in older AML patients unsuitable for intensive therapy. Eighty‐three patients were randomised to the study. An overall response rate was seen in 19.5% (all complete remission [CR]) and 15% (7.5% each in CR and CR without evidence of adequate count recovery [CRi]) of patients in the LDAC+BCT‐100 and LDAC arms respectively (odds ratio 0.73, confidence interval 0.23–2.33; p = 0.592). No significant difference in overall or median survival between treatment arms was seen. The addition of BCT‐100 to LDAC was well tolerated.