SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors
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....
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Impact Journals
2016
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/49786/ |
| _version_ | 1848798077569204224 |
|---|---|
| author | Xue, Wei Brentville, Victoria A. Symonds, Peter Cook, Katherine Yagita, Hideo Metheringham, Rachael L. Durrant, Lindy |
| author_facet | Xue, Wei Brentville, Victoria A. Symonds, Peter Cook, Katherine Yagita, Hideo Metheringham, Rachael L. Durrant, Lindy |
| author_sort | Xue, Wei |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:14:02Z |
| format | Article |
| id | nottingham-49786 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:14:02Z |
| publishDate | 2016 |
| publisher | Impact Journals |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-497862020-05-04T18:22:30Z https://eprints.nottingham.ac.uk/49786/ 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 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. Impact Journals 2016-11-04 Article PeerReviewed Xue, Wei, Brentville, Victoria A., Symonds, Peter, Cook, Katherine, Yagita, Hideo, Metheringham, Rachael L. and Durrant, Lindy (2016) SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors. Oncotarget, 7 (50). pp. 83088-83100. ISSN 1949-2553 DNA vaccine; Fc targeting; PD-1 blockade; melanoma; tumor rejection http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=13070&path[]=41414 doi:10.18632/oncotarget.13070 doi:10.18632/oncotarget.13070 |
| spellingShingle | DNA vaccine; Fc targeting; PD-1 blockade; melanoma; tumor rejection Xue, Wei Brentville, Victoria A. Symonds, Peter Cook, Katherine Yagita, Hideo Metheringham, Rachael L. Durrant, Lindy SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors |
| title | SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors |
| title_full | SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors |
| title_fullStr | SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors |
| title_full_unstemmed | SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors |
| title_short | SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors |
| title_sort | scib1, a huigg1 antibody dna vaccination, combined with pd-1 blockade induced efficient therapy of poorly immunogenic tumors |
| topic | DNA vaccine; Fc targeting; PD-1 blockade; melanoma; tumor rejection |
| url | https://eprints.nottingham.ac.uk/49786/ https://eprints.nottingham.ac.uk/49786/ https://eprints.nottingham.ac.uk/49786/ |