Tumor suppression of novel anti-PD-1 antibodies mediated through CD28 costimulatory pathway.

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Version: Final published version
License: CC BY-NC-SA 4.0
Serval ID
serval:BIB_0B420592FE76
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tumor suppression of novel anti-PD-1 antibodies mediated through CD28 costimulatory pathway.
Journal
The Journal of experimental medicine
Author(s)
Fenwick C., Loredo-Varela J.L., Joo V., Pellaton C., Farina A., Rajah N., Esteves-Leuenberger L., Decaillon T., Suffiotti M., Noto A., Ohmiti K., Gottardo R., Weissenhorn W., Pantaleo G.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
01/07/2019
Peer-reviewed
Oui
Volume
216
Number
7
Pages
1525-1541
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Classical antagonistic antibodies (Abs) targeting PD-1, such as pembrolizumab and nivolumab, act through blockade of the PD-1-PDL-1 interaction. Here, we have identified novel antagonistic anti-PD-1 Abs not blocking the PD-1-PDL-1 interaction. The nonblocking Abs recognize epitopes on PD-1 located on the opposing face of the PDL-1 interaction and overlap with a newly identified evolutionarily conserved patch. These nonblocking Abs act predominantly through the CD28 coreceptor. Importantly, a combination of blocking and nonblocking Abs synergize in the functional recovery of antigen-specific exhausted CD8 T cells. Interestingly, nonblocking anti-PD-1 Abs have equivalent antitumor activity compared with blocker Abs in two mouse tumor models, and combination therapy using both classes of Abs enhanced tumor suppression in the mouse immunogenic tumor model. The identification of the novel nonblocker anti-PD-1 Abs and their synergy with classical blocker Abs may be instrumental in potentiating immunotherapy strategies and antitumor activity.
Keywords
Animals, Antineoplastic Agents, Immunological/immunology, Antineoplastic Agents, Immunological/therapeutic use, CD28 Antigens/metabolism, CD8-Positive T-Lymphocytes/immunology, Epitopes/immunology, Humans, Jurkat Cells, Mice, NF-kappa B/metabolism, Neoplasms, Experimental/immunology, Neoplasms, Experimental/therapy, Programmed Cell Death 1 Receptor/immunology, Proto-Oncogene Proteins c-akt/metabolism, Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2019 17:59
Last modification date
15/01/2021 8:08
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