Inhaled dry powder cisplatin increases antitumour response to anti-PD1 in a murine lung cancer model.
Chemotherapy
DPI
Dry powder for inhalation
Immune checkpoint inhibitor
NSCLC
PD-L1
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
07
09
2022
revised:
28
11
2022
accepted:
30
11
2022
pubmed:
6
12
2022
medline:
3
2
2023
entrez:
5
12
2022
Statut:
ppublish
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.
Identifiants
pubmed: 36470334
pii: S0168-3659(22)00809-4
doi: 10.1016/j.jconrel.2022.11.055
pii:
doi:
Substances chimiques
Cisplatin
Q20Q21Q62J
Powders
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
317-326Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K. Amighi, N. Wauthoz, and R. Rosière are inventors of patents related to some technologies described in the paper and are co-founders of InhaTarget Therapeutics. R. Rosière is also the CSO of InhaTarget Therapeutics and a scientific collaborator of the Unit of Pharmaceutics and Biopharmaceutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.