Naslov
Combined anti-VEGF and anti-PD-L1 immune checkpoint therapy of SCLC significantly improved progression-free and overall survival

Autori
Meder, Lydia ; Schuldt, Philipp ; Wennhold, Kerstin ; Schlößer, Hans A. ; Vlašić, Ignacija ; Florin, Alexandra ; Bergwelt-Baildon, Michael von ; Odenthal, Margarete ; Buettner, Reinhard ; Wolf, Juergen ; Hallek, Michael ; Reinhardt, H. Christian ; Ullrich, T. Roland.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Precision oncology: Translating basic discoveries into patient survival. / - , 2016, 37-37

Skup
32nd Ernst Klenk Symposium in Molecular Medicine

Mjesto i datum
Njemačka, 08.12.2016. - 10.12.2016

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
VEGF ; PD-L1 ; immune checkpoint therapy ; SCLC

Sažetak
Lung cancer is the leading cause of smoking- and cancer-related deaths worldwide. Small cell lung carcinomas (SCLC) account for approximately 14 % of all lung cancer cases and are frequently diagnosed at late stage with a median survival of 9 months. Novel therapy approaches including ‘programmed cell death receptor 1’ (PD1) and ‘programmed cell death ligand 1’ (PD-L1) blockade revealed compelling anti-Tumor immunity in several cancers such as melanomas and lung carcinomas. Here, we aimed to decipher the efficacy of PD-L1 alone and in combination with anti-‘vascular endothelial growth factor’ (VEGF) targeted treatment in a transgenic mouse model of SCLC. We used the genetically engineered SCLC mouse model to investigate the effect of combined anti-VEGF/anti-PD-L1 therapy on progression-free survival (PFS), overall survival (OS) and tumor-associated immune cells. We found that combined anti-VEGF/anti-PD-L1 targeted therapy significantly improved PFS and OS of mice compared to vehicle, anti-PD-L1 and anti-VEGF monotherapy. Mice treated with anti-PD-L1 alone relapsed after 3 to 4 weeks of treatment presenting an exhausted T cell phenotype indicated by an increase in tumorassociated PD1 and TIM3 expressing CD4 and CD8 T cells. Strikingly, this exhausted phenotype was abrogated in mice treated with combined anti-VEGF and anti-PD-L1 antibodies. Our data suggest potential synergistic effects by combining anti-VEGF and anti-PD-L1 targeted treatment in SCLC. In order to investigate our findings in the clinic, we will analyze biopsies and peripheral blood from SCLC patients treated with standard therapies and will compare them to refractory SCLCs treated with anti-immune checkpoint therapies. Finally, whole exome and RNA sequencing of selected cases will be performed to identify biomarkers of response and alternative resistance mechanisms.

Izvorni jezik
Engleski

POVEZANOST RADA