Inhaled cisplatin dry powder combined with anti-PD1 induces anti-tumour immune-response in lung cancer
Tamara Davenne1,2,3, Pauline Lehebel1, Lionel Larbanoix4, Muriel Moser3, Oberdan Leo3, Etienne Meylan3, Nathalie Wauthoz2, Stanislas Goriely3, Karim Amighi2 and Rémi Rosière1,2
1InhaTarget Therapeutics, Rue Antoine de Saint Exupéry 2, 6041 Gosselies, Belgium
2Unit of Pharmaceutics and Biopharmaceutics, Université libre de Bruxelles (ULB), boulevard du triomphe, Campus plaine CP207, 1050 Brussels, Belgium
3 Laboratory of Immunobiology, U-CRI, Rue Adrienne Boland 10, 6041, Gosselies Belgium
4Center for Microscopy and Molecular Imaging (CMMI), Université de Mons, 6041 Gosselies, Belgium
Summary
Despite advances in targeted therapies and immunotherapy in non-small cell lung cancer (NSCLC), intravenous chemotherapy, and its numerous side effects, remains the backbone of NSCLC treatment. Inhaled chemotherapy addresses the problem of systemic toxicities observed with intravenous administration and increased local concentrations. Dry powder cisplatin for inhalation (CIS-DPI) was tested as a novel way to deliver cisplatin locally via the pulmonary route, to target lung tumours. CIS-DPI delivered by endotracheal administration demonstrated a dose dependent efficacy in the syngeneic orthotopic M109 lung carcinoma murine model. In addition, CIS-DPI induced an upregulation of the immune checkpoint PD-L1 on tumour cells, suggesting an additional benefit when combined with an immune checkpoint inhibitor. Indeed, the combination of CIS-DPI with anti-PD1 therapy significantly reduced tumour growth and prolonged survival compared to anti-PD1 monotherapy. In the tumour, the combination treatment induced the most potent recruitment of conventional dendritic cells and of tumour infiltrating lymphocytes, showing the hallmarks of an anti-tumour immune response. Altogether, our results show the efficient pulmonary delivery of CIS-DPI exerting its direct cytotoxic effect on tumour, and its additional effect on the anti-tumour immune response when combined with anti-PD1 therapy. Thus, combining CIS-DPI with anti-PD1 is a promising strategy for improved lung cancer therapy.
Key Message
Cisplatin dry powder delivered by inhalation in vivo induces tumour shrinkage and prolongs survival. Its combination with anti-PD1 also enhanced the anti-tumour immune response. By addressing intravenous chemotherapy limitations, inhaled cisplatin with a dry powder inhaler promises enhanced efficacy, reduced side effects and potential for self-medication at home for lung cancer patients.