Challenges in neoantigen-directed therapeutics

Lien Lybaert; Steve Lefever; Bruno Fant; Evelien Smits; Bruno De Geest; Karine Breckpot; Luc Dirix; Steven A Feldman; Wim van Criekinge; Kris Thielemans; Sjoerd H van der Burg; Patrick A Ott; Cedric Bogaert

doi:10.1016/j.ccell.2022.10.013

Challenges in neoantigen-directed therapeutics

Cancer Cell. 2023 Jan 9;41(1):15-40. doi: 10.1016/j.ccell.2022.10.013. Epub 2022 Nov 10.

Authors

Affiliations

¹ myNEO NV, 9000 Ghent, Belgium.
² Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium.
³ Department of Pharmaceutics, Ghent University, 9000 Ghent, Belgium.
⁴ Laboratory of Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
⁵ Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
⁶ Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Department of Data Analysis and Mathematical Modelling, Ghent University, Ghent, Belgium.
⁸ Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands.
⁹ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
¹⁰ myNEO NV, 9000 Ghent, Belgium. Electronic address: [email protected].

PMID: 36368320
DOI: 10.1016/j.ccell.2022.10.013

Abstract

A fundamental prerequisite for the efficacy of cancer immunotherapy is the presence of functional, antigen-specific T cells within the tumor. Neoantigen-directed therapy is a promising strategy that aims at targeting the host's immune response against tumor-specific antigens, thereby eradicating cancer cells. Initial forays have been made in clinical environments utilizing vaccines and adoptive cell therapy; however, many challenges lie ahead. We provide an in-depth overview of the current state of the field with an emphasis on in silico neoantigen discovery and the clinical aspects that need to be addressed to unlock the full potential of this therapy.

Keywords: cancer; immunotherapy; neoantigen; vaccine.

Publication types

Review
Comment

MeSH terms

Antigens, Neoplasm
Cancer Vaccines* / therapeutic use
Humans
Immunotherapy
Neoplasms* / drug therapy
T-Lymphocytes

Substances

Cancer Vaccines
Antigens, Neoplasm