Anti-mouse-PD-1-CD279-Clone-29F_1A12FB-1

AUTHORS

Peng Liu, Liwei Zhao, Jonathan Pol, Sarah Levesque, Adriana Petrazzuolo, Christina Pfirschke, Camilla Engblom, Steffen Rickelt, Takahiro Yamazaki, Kristina Iribarren, Laura Senovilla, Lucillia Bezu, Erika Vacchelli, Valentina Sica, AndrĆ©a Melis, Tiffany Martin, Lin Xia, Heng Yang, Qingqing Li, Jinfeng Chen, SylvĆØre Durand, Fanny Aprahamian, Deborah Lefevre, Sophie Broutin, Angelo Paci, Amaury Bongers, Veronique Minard-Colin, Eric Tartour, Laurence Zitvogel, Lionel Apetoh, Yuting Ma, Mikael J. Pittet, Oliver Kepp & Guido Kroemer

 

SUMMARY

Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10ā€‰ĀµM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-Ī³ neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.

REFERENCES

Liu, P., Zhao, L., Pol, J. et al. Crizotinib-induced immunogenic cell death in non-small cell lung cancer. Nat Commun 10, 1486 (2019). https://doi.org/10.1038/s41467-019-09415-3

PRODUCT HIGHLIGHTS

The following Bio X Cell in vivo monoclonal antibodies were featured in the publication: