Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors
Open Access
- 3 November 2016
- Vol. 4 (4), 37
- https://doi.org/10.3390/vaccines4040037
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.This publication has 146 references indexed in Scilit:
- Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical SignificanceCancer Microenvironment, 2012
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- Active Immunotherapy Combined With Blockade of a Coinhibitory Pathway Achieves Regression of Large Tumor Masses in Cancer-prone MiceMolecular Therapy, 2011
- VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responsesThe Journal of Experimental Medicine, 2011
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaThe New England Journal of Medicine, 2010
- Sipuleucel-T Immunotherapy for Castration-Resistant Prostate CancerThe New England Journal of Medicine, 2010
- PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumorsProceedings of the National Academy of Sciences of the United States of America, 2010
- OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosisThe Journal of Experimental Medicine, 2009
- CTLA-4 blockade increases IFNγ-producing CD4 + ICOS hi cells to shift the ratio of effector to regulatory T cells in cancer patientsProceedings of the National Academy of Sciences of the United States of America, 2008
- CTLA-4 Blockade Confers Lymphocyte Resistance to Regulatory T-Cells in Advanced Melanoma: Surrogate Marker of Efficacy of Tremelimumab?Clinical Cancer Research, 2008