Pulmonary macrophage transplantation (PMT) therapy via a lentiviral vector
Treatment for hereditary Pulmonary Alveolar Proteinosis (hPAP)
hPAP pathogenesis is driven by disruption of GM-CSF signaling to alveolar macrophages, which impairs GM-CSF-dependent surfactant clearance. Using GM-CSF receptor-β deficient (Csf2rb−/−) mice that develop a myeloid cell disorder identical to hPAP in children with CSF2RA/CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe, well-tolerated, and that one administration corrected the lung disease, secondary systemic manifestations, normalized disease-related biomarkers, and prevented disease-specific mortality. Our results demonstrate that a single PMT of macrophages bearing functional GM-CSF receptors resulted in macrophage engraftment and therapeutic efficacy in a PAP mouse model. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects.
First specific therapy for children with hPAP.
- Organ-targeted, non-stem cell transfer without radiation or chemotherapy.
- One dose resolved lung and systemic abnormalities.
- Extraordinary efficacy due to selective survival advantage.
- Well tolerated and safe.
hPAP is a rare disease with an estimated frequency of 0.5 per 100,000 persons.
Bruce C. Trapnell, MS, MD, Director, Transitional Pulmonary Science Center