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

Challenges in neoantigen-directed therapeutics

Lien Lybaert  1 , Steve Lefever  1 , Bruno Fant  1 , Evelien Smits  2 , Bruno De Geest  3 , Karine Breckpot  4 , Luc Dirix  5 , Steven A Feldman  6 , Wim van Criekinge  7 , Kris Thielemans  4 , Sjoerd H van der Burg  8 , Patrick A Ott  9 , Cedric Bogaert  10
Affiliations
Free article
Review

Challenges in neoantigen-directed therapeutics

Lien Lybaert et al. Cancer Cell. .
Free article

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.

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Conflict of interest statement

Declaration of interests L.L., S.L., and B.F. are employees and shareholders at myNEO NV. E.S. is a member of the scientific advisory board of Intra-Vacc. W.v.C. is co-founder and shareholder at myNEO NV. K.T. is a scientific founder of and holds equity in eTheRNA Immunotherapies, and is member of the scientific advisory board of myNEO NV. S.H.v.d.B. is named as inventor on the patent for the use of synthetic long peptides as vaccine as well as on a patent for TEIPP neoantigen-specific treatments. He also serves as a paid member of the strategy board of the vaccine companies: ISA Pharmaceuticals, PCI Biotech, DCprime, and AGLAIA, and also performs contract research on neoantigens for Enara BIO and Frame Pharmaceuticals. P.A.O. reports research funding from and has advised Neon Therapeutics, Bristol-Meyers Squibb, Medrck, CytomX, Pfizer, Novartis, Celldex, Amgen, Array, AstraZeneca/MedImmune, Armo BioSciences, Xencor, Oncorus, and Roche/Genentech. C.B. is co-founder and shareholder at myNEO NV.

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