Shared neoantigens for cancer immunotherapy

Exploration of neoantigens holds the potential to be productive in immuno-oncotherapy. Among tumor-specific antigens, neoantigens result from genetic instability that gives rise to non-synonymous somatic mutations, highly specific to tumor cells. In addition to point mutations, gene rearrangements,...

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Main Authors: Anastasia Goloudina, Fabien Le Chevalier, Pierre Authié, Pierre Charneau, Laleh Majlessi
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Molecular Therapy: Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950329925000475
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author Anastasia Goloudina
Fabien Le Chevalier
Pierre Authié
Pierre Charneau
Laleh Majlessi
author_facet Anastasia Goloudina
Fabien Le Chevalier
Pierre Authié
Pierre Charneau
Laleh Majlessi
author_sort Anastasia Goloudina
collection DOAJ
description Exploration of neoantigens holds the potential to be productive in immuno-oncotherapy. Among tumor-specific antigens, neoantigens result from genetic instability that gives rise to non-synonymous somatic mutations, highly specific to tumor cells. In addition to point mutations, gene rearrangements, indels leading to frameshifts, chromosomal translocations or inversions that may lead to fusion proteins, alternative mRNA splicing, and integration of genetic material of oncogenic viruses into the host genome provide consistent sources of neoantigens that are absent in healthy tissues. Out of these alterations, 2%–3% may generate T cell neoepitopes, possibly detectable by TCRs. Neoantigens are absent in healthy tissues and are thus at low risk of triggering autoimmunity. In addition, the host lymphocytes have not been rendered tolerant toward them and it is possible to induce immune responses against them. Here, we overview the two categories of neoantigens, i.e., private and shared, and their use in immuno-oncotherapy in selected pre-clinical and clinical studies. The vast majority of commonly occurring tumor-specific mutations are cancer causing and are permanently expressed by all malignant tumor cells, preventing the latter from escaping vaccine-induced anti-neoantigen immunity. The use of public neoantigens combined with efficient vaccine platforms can provide non-personalized “off-the-shelf” therapeutic vaccine candidates for broad-spectrum immunotherapy purposes.
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spelling doaj-art-e7e068e026ba49229cd83c69fa47def42025-08-20T03:08:47ZengElsevierMolecular Therapy: Oncology2950-32992025-06-0133220097810.1016/j.omton.2025.200978Shared neoantigens for cancer immunotherapyAnastasia Goloudina0Fabien Le Chevalier1Pierre Authié2Pierre Charneau3Laleh Majlessi4Pasteur-TheraVectys Joint Lab, Institut Pasteur, Université de Paris, Virology Department, 28 rue du Dr. Roux, 75015 Paris, FrancePasteur-TheraVectys Joint Lab, Institut Pasteur, Université de Paris, Virology Department, 28 rue du Dr. Roux, 75015 Paris, FrancePasteur-TheraVectys Joint Lab, Institut Pasteur, Université de Paris, Virology Department, 28 rue du Dr. Roux, 75015 Paris, FrancePasteur-TheraVectys Joint Lab, Institut Pasteur, Université de Paris, Virology Department, 28 rue du Dr. Roux, 75015 Paris, FrancePasteur-TheraVectys Joint Lab, Institut Pasteur, Université de Paris, Virology Department, 28 rue du Dr. Roux, 75015 Paris, France; Corresponding author: Laleh Majlessi, Pasteur-TheraVectys Joint Lab, Institut Pasteur, Université de Paris, Virology Department, 28 rue du Dr. Roux, Paris 75015, France.Exploration of neoantigens holds the potential to be productive in immuno-oncotherapy. Among tumor-specific antigens, neoantigens result from genetic instability that gives rise to non-synonymous somatic mutations, highly specific to tumor cells. In addition to point mutations, gene rearrangements, indels leading to frameshifts, chromosomal translocations or inversions that may lead to fusion proteins, alternative mRNA splicing, and integration of genetic material of oncogenic viruses into the host genome provide consistent sources of neoantigens that are absent in healthy tissues. Out of these alterations, 2%–3% may generate T cell neoepitopes, possibly detectable by TCRs. Neoantigens are absent in healthy tissues and are thus at low risk of triggering autoimmunity. In addition, the host lymphocytes have not been rendered tolerant toward them and it is possible to induce immune responses against them. Here, we overview the two categories of neoantigens, i.e., private and shared, and their use in immuno-oncotherapy in selected pre-clinical and clinical studies. The vast majority of commonly occurring tumor-specific mutations are cancer causing and are permanently expressed by all malignant tumor cells, preventing the latter from escaping vaccine-induced anti-neoantigen immunity. The use of public neoantigens combined with efficient vaccine platforms can provide non-personalized “off-the-shelf” therapeutic vaccine candidates for broad-spectrum immunotherapy purposes.http://www.sciencedirect.com/science/article/pii/S2950329925000475MT: Regular Issueneoantigensneoepitopespersonal neoantigensshared neoantigensmutations
spellingShingle Anastasia Goloudina
Fabien Le Chevalier
Pierre Authié
Pierre Charneau
Laleh Majlessi
Shared neoantigens for cancer immunotherapy
Molecular Therapy: Oncology
MT: Regular Issue
neoantigens
neoepitopes
personal neoantigens
shared neoantigens
mutations
title Shared neoantigens for cancer immunotherapy
title_full Shared neoantigens for cancer immunotherapy
title_fullStr Shared neoantigens for cancer immunotherapy
title_full_unstemmed Shared neoantigens for cancer immunotherapy
title_short Shared neoantigens for cancer immunotherapy
title_sort shared neoantigens for cancer immunotherapy
topic MT: Regular Issue
neoantigens
neoepitopes
personal neoantigens
shared neoantigens
mutations
url http://www.sciencedirect.com/science/article/pii/S2950329925000475
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