US EPA

3993855 

Journal Article 

Treatment with a programmed cell death-1-specific antibody has little effect on afatinib- and naphthalene-induced acute pneumonitis in mice 

Hamada, N; Yanagihara, T; Suzuki, K; Ogata-Suetsugu, S; Harada, E; Mikumo, H; Arimura-Omori, M; Nakanishi, Y 

2017 

Yes 

Biochemical and Biophysical Research Communications
ISSN: 0006-291X
EISSN: 1090-2104 

491 

3 

656-661 

English 

28756224 

10.1016/j.bbrc.2017.07.148 

WOS:000410876900014 

https://www.proquest.com/scholarly-journals/treatment-with-programmed-cell-death-1-specific/docview/2067282002/se-2
Exit
 

Although several antibodies developed to target programmed cell death-1 (PD-1) and its ligand (PD-L1) have demonstrated great promise for the treatment of non-small cell lung cancer (NSCLC), and other malignancies, these therapeutic antibodies can cause pneumonitis. Furthermore, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced pneumonitis was reported after treatment with anti PD-1 antibodies. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis through a neutrophil-dependent mechanism. The present study aimed to investigate whether treatment with afatinib, an EGFR-TKI that effectively targets EGFR mutation-positive NSCLC, and anti PD-1 antibodies induces pneumonitis in mice. C57BL/6J mice were treated intraperitoneally with naphthalene (200 mg/kg) on day 0. Afatinib (20 mg/kg) was administered orally on days -1 to 13. An anti-PD-1 antibody (0.2 mg/mice) was also administered intraperitoneally every 3 days from day 1 until day 13. The bronchoalveolar lavage fluid (BALF) and lung tissues were sampled on day 14. As observed previously with gefitinib, afatinib significantly increased the severity of histopathologic findings and the level of protein in BALF on day 14, compared to treatment with naphthalene alone. A combined anti-PD-1 antibody and afatinib treatment after naphthalene administration had yielded the same histopathological grade of lung inflammation as did afatinib treatment alone. Our results suggest that anti-PD-1 antibody treatment has little effect on afatinib-induced lung injury. 

Acute pneumonitis; Afatinib; Anti PD-1 antibody; EGFR-TKI; Immune checkpoint inhibitor; article; antibodies; enzyme inhibitors; epidermal growth factor; epithelium; histopathology; inflammation; ligands; lung neoplasms; naphthalene; pneumonia