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Inhaled dry powder cisplatin increases antitumour response to anti-PD1 in a murine lung cancer model

par Davenne, Tamara ;Percier, Pauline;Larbanoix, Lionel;Moser, Muriel ;Leo, Oberdan ;Meylan, Etienne ;Goriely, Stanislas ;Gérard, Pierre;Wauthoz, Nathalie ;Laurent, Sophie;Amighi, Karim ;Rosiere, Rémi
Référence Journal of controlled release, 353, page (317-326)
Publication Publié, 2022-12-06

Article révisé par les pairs

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Résumé :

Despite advances in targeted therapies and immunotherapy in lung cancer, chemotherapy remains the backbone of treatment in most patients at different stages of the disease. Inhaled chemotherapy is a promising strategy to target lung tumours and to limit the induced severe systemic toxicities. Cisplatin dry powder for inhalation (CIS-DPI) was tested as an innovative way to deliver cisplatin locally via the pulmonary route with minimal systemic toxicities. In vivo, CIS-DPI demonstrated a dose-dependent antiproliferative activity in the M109 orthotopic murine lung tumour model and upregulated the immune checkpoint PD-L1 on lung tumour cells. Combination of CIS-DPI with the immune checkpoint inhibitor anti-PD1 showed significantly reduced tumour size, increased the number of responders and prolonged median survival over time in comparison to the anti-PD1 monotherapy. Furthermore, the CIS-DPI and anti-PD1 combination induced an intra-tumour recruitment of conventional dendritic cells and tumour infiltrating lymphocytes, highlighting an anti-tumour immune response. This study demonstrates that combining CIS-DPI with anti-PD1 is a promising strategy to improve lung cancer therapy.