Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors.
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.
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, 75015 Paris, France. soumaya.karaki@inserm.fr.
Soumaya
S
Karaki
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, 75015 Paris, France. marie.anson@inserm.fr.
Marie
M
Anson
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, 75015 Paris, France. thi.tran@inserm.fr.
Thi
T
Tran
Hôpital Européen Georges Pompidou, AP-HP, Service d'Immunologie biologique, 75015 Paris, France. delphine.giusti@aphp.fr.
Delphine
D
Giusti
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, 75015 Paris, France. Charlotte.blanc@gmail.com.
Charlotte
C
Blanc
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, 75015 Paris, France. stephane.oudard@aphp.fr.|Department of Oncology, Hôpital Européen Georges Pompidou, 75015 Paris, France. stephane.oudard@aphp.fr.
Stephane
S
Oudard
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, 75015 Paris, France. eric.tartour@aphp.fr.|Hôpital Européen Georges Pompidou, AP-HP, Service d'Immunologie biologique, 75015 Paris, France. eric.tartour@aphp.fr.|Equipe Labellisée Ligue contre le Cancer, 75015.Paris, France. eric.tartour@aphp.fr.
Eric
E
Tartour
CD40; CTLA-4; OX40; PD-1; PD-L1; cancer vaccine; checkpoint inhibitors; combination therapy; immunotherapy