SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors
Xue, Wei; Brentville, Victoria A.; Symonds, Peter; Cook, Katherine; Yagita, Hideo; Metheringham, Rachael L.; Durrant, Lindy
Victoria A. Brentville
Rachael L. Metheringham
Purpose: We have previously shown that supraoptimal signaling of high avidity T cells leads to high expression of PD-1 and inhibition of proliferation. This study was designed to see if this effect could be mitigated by combining a vaccine that stimulates high avidity T cells with PD-1 blockade.
Experimental Design: We investigated the anti-tumor effect of a huIgG1 antibody DNA vaccine (SCIB1) and PD-1 blockade.
Results: Vaccination of HLA-DR4 transgenic mice with SCIB1 induced high frequency and avidity T cell responses that resulted in survival (40%) of mice with established B16F1-DR4 tumors. SCIB1 vaccination was associated with increased infiltration of CD4 and CD8 T cells within the tumor but was also associated with upregulation of PD-L1 within the tumor environment. PD-1 blockade also resulted in increased CD8 T cell infiltration and an anti-tumor response with 50% of mice showing long term survival. In line with our hypothesis that PD-1/PD-L1 signaling results in inhibition of proliferation of high avidity T cells at the tumor site, the combination of PD-1 blockade with vaccination, enhanced the number and proliferation of the CD8 tumor infiltrate. This resulted in a potent anti-tumor response with 80% survival of the mice.
Conclusions: There is a benefit in combining PD-1 blockade with vaccines that induce high avidity T cell responses and in particular with SCIB1.
Xue, W., Brentville, V. A., Symonds, P., Cook, K., Yagita, H., Metheringham, R. L., & Durrant, L. (in press). SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors. Oncotarget, 7(50), https://doi.org/10.18632/oncotarget.13070
|Journal Article Type||Article|
|Acceptance Date||Sep 24, 2016|
|Online Publication Date||Nov 4, 2016|
|Deposit Date||Feb 15, 2018|
|Publicly Available Date||Feb 15, 2018|
|Peer Reviewed||Peer Reviewed|
|Keywords||DNA vaccine; Fc targeting; PD-1 blockade; melanoma; tumor rejection|
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0