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Vaccines 2016, 4(4), 37; doi:10.3390/vaccines4040037

Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors

1
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, 75015 Paris, France
2
Hôpital Européen Georges Pompidou, AP-HP, Service d’Immunologie biologique, 75015 Paris, France
3
Department of Oncology, Hôpital Européen Georges Pompidou, 75015 Paris, France
4
Equipe Labellisée Ligue contre le Cancer, 75015.Paris, France
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Walter Storkus
Received: 27 August 2016 / Revised: 23 October 2016 / Accepted: 31 October 2016 / Published: 3 November 2016
(This article belongs to the Special Issue Mechanisms of Tumor Escape from Host Immunity)
View Full-Text   |   Download PDF [731 KB, uploaded 15 November 2016]   |  

Abstract

Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%–80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86). Enhanced T cell infiltration of various tumors has been demonstrated following this combination therapy. The timing of this combination appears to be critical to the success of this therapy and multiple combinations of immunomodulating antibodies (CPI antagonists or costimulatory pathway agonists) have reinforced the synergy with cancer vaccines. Only limited results are available in humans and this combined approach has yet to be validated. Comprehensive monitoring of the regulation of CPI and costimulatory molecules after administration of immunomodulatory antibodies (anti-PD1/PD-L1, anti-CTLA-4, anti-OX40, etc.) and cancer vaccines should help to guide the selection of the best combination and timing of this therapy. View Full-Text
Keywords: cancer vaccine; checkpoint inhibitors; immunotherapy; combination therapy; PD-1; PD-L1; CTLA-4; CD40; OX40 cancer vaccine; checkpoint inhibitors; immunotherapy; combination therapy; PD-1; PD-L1; CTLA-4; CD40; OX40
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Karaki, S.; Anson, M.; Tran, T.; Giusti, D.; Blanc, C.; Oudard, S.; Tartour, E. Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors. Vaccines 2016, 4, 37.

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