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Attacking Tumors From All Sides: Personalized Multiplex Vaccines to Tackle Intratumor Heterogeneity

Authors :
Felix L. Fennemann
I. Jolanda M. de Vries
Carl G. Figdor
Martijn Verdoes
Source :
Frontiers in Immunology, Vol 10 (2019)
Publication Year :
2019
Publisher :
Frontiers Media S.A., 2019.

Abstract

Tumor vaccines are an important asset in the field of cancer immunotherapy. Whether prophylactic or therapeutic, these vaccines aim to enhance the T cell-mediated anti-tumor immune response that is orchestrated by dendritic cells. Although promising preclinical and early-stage clinical results have been obtained, large-scale clinical implementation of cancer vaccination is stagnating due to poor clinical response. The challenges of clinical efficacy of tumor vaccines can be mainly attributed to tumor induced immunosuppression and poor immunogenicity of the chosen tumor antigens. Recently, intratumor heterogeneity and the relation with tumor-specific neoantigen clonality were put in the equation.In this perspective we provide an overview of recent studies showing how personalized tumor vaccines containing multiple neoantigens can broaden and enhance the anti-tumor immune response. Furthermore, we summarize advances in the understanding of the intratumor mutational landscape containing different tumor cell subclones and the temporal and spatial diversity of neoantigen presentation and burden, and the relation between these factors with respect to tumor immunogenicity. Together, the presented knowledge calls for the investment in the characterization of neoantigens in the context of intratumor heterogeneity to improve clinical efficacy of personalized tumor vaccines.

Details

Language :
English
ISSN :
16643224
Volume :
10
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.1115dc8d9f742cb86d862275a3be1bd
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2019.00824