Empowering therapeutic antibodies with IFN-α for cancer immunotherapy

• DOI: 10.1371/journal.pone.0219829
• Publication Date: 2019-08-08T17:47:23Z
• Authors: Jun Guo; Yu Xiao; Ramesh Iyer; Xin Lu; Marc Lake; Uri Ladror; John Harlan; Tanushree Samanta; Medha Tomlinson; Gail Bukofzer; Cherrie Donawho; Alex Shoemaker; Tzu-Hsuan Huang
• Keywords: Cancer Immunotherapy

Type 1 IFNs stimulate secretion of IP-10 (CXCL10) which is a critical chemokine to recruit effector T cells the tumor microenvironment and knockout mice exhibit phenotype with compromised cell generation trafficking. also induce MHC class upregulation on can enhance anti-tumor CD8 response in microenvironment. Although type show great promise potentiating immune response, systemic delivery associated toxicity thereby limiting clinical application. In this study, we fused targeting antibodies IFN-α showed that fusion proteins be produced high yields purity. IFN fusions selectively induced from antigen positive cells, was recruiting Further, found treatment anti-PDL1-IFN- α at concentrations as low pM exhibited potent activity mediating OT1 CD8+ killing against OVA expressing while control did not any same concentration. Furthermore, antibody well tolerated vivo demonstrated efficacy an anti-PD-L1 resistant syngeneic mouse model. One potential mechanisms for enhanced by up-regulation I/tumor complex. Our data supports hypothesis may functions response.