Computational Methods for Identification of T Cell Neoepitopes in Tumors

Jurtz, Vanessa Isabell; Olsen, Lars Rønn

doi:10.1007/978-1-4939-8868-6_9

Cited by 10 publications

(6 citation statements)

References 74 publications

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“…Of note, the performance of variant calling algorithms is directly related to the process of sequencing. Thus, current technical limitations of sequencing technology such as errors introduced by PCR amplification during library construction or mismapped reads can affect the accurate identification of somatic variants leading to detection of false variants (41). Tumor heterogeneity is an additional limitation for calling somatic variants with confidence, since it biases the detection of clonal over subclonal mutations due to differences in variant allele frequency, thus resulting in underrepresentation of somatic variants (41).…”

Section: Identification Of Candidate Neoantigensmentioning

confidence: 99%

Determinants for Neoantigen Identification

2019

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All tumors accumulate genetic alterations, some of which can give rise to mutated, non-self peptides presented by human leukocyte antigen (HLA) molecules and elicit T-cell responses. These immunogenic mutated peptides, or neoantigens, are foreign in nature and display exquisite tumor specificity. The correlative evidence suggesting they play an important role in the effectiveness of various cancer immunotherapies has triggered the development of vaccines and adoptive T-cell therapies targeting them. However, the systematic identification of personalized neoantigens in cancer patients, a critical requisite for the success of these therapies, remains challenging. A growing amount of evidence supports that only a small fraction of all tumor somatic non-synonymous mutations (NSM) identified represent bona fide neoantigens; mutated peptides that are processed, presented on the cell surface HLA molecules of cancer cells and are capable of triggering immune responses in patients. Here, we provide an overview of the existing strategies to identify candidate neoantigens and to evaluate their immunogenicity, two factors that impact on neoantigen identification. We will focus on their strengths and limitations to allow readers to rationally select and apply the most suitable method for their specific laboratory setting.

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Section: Identification Of Candidate Neoantigensmentioning

confidence: 99%

Determinants for Neoantigen Identification

2019

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“…In the WES data-based strategy, unfiltered candidate neoepitopes are listed and identified. However, there is a high success rate for tumors with a high mutation load [ 15 ]. Mass spectrometry (MS)-based immunopeptidomics is another technique which not only provides the characterization of post-translational modified peptides and non-canonical neoepitopes but also directly identifies naturally presented HLA-bound peptides [ 16 , 17 ].…”

Section: Neoepitopesmentioning

confidence: 99%

TCR-like CARs and TCR-CARs targeting neoepitopes: an emerging potential

et al. 2021

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Neoepitopes or neoantigens are a spectrum of unique mutations presented in a particular patient’s tumor. Neoepitope-based adoptive therapies have the potential of tumor eradication without undue damaging effect on normal tissues. In this context, methods based on the T cell receptor (TCR) engineering or chimeric antigen receptors (CARs) have shown great promise. This review focuses on the TCR-like CARs and TCR-CARs directed against tumor-derived epitopes, with a concerted view on neoepitopes. We also address the current limitations of the field to know how to harness the full benefits of this approach and thereby design a sustained and specific antitumor therapy.

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“…Two or more variant calling algorithms are employed to limit false positives [79,80]. However, there is a need to improve the sensitivity of these algorithms because one problem with this approach is the presence of false negatives, somatic variants that remain undetected [81]. An alternative strategy employed for the identification of neoantigens is RNA sequencing (RNA-seq), which is used in combination with WES/WGS to select the predicted mutations that are expressed as RNA and thus considered for further analysis [82].…”

Section: New Technologies For Neoantigens Discoverymentioning

confidence: 99%

Tumor antigens heterogeneity and immune response-targeting neoantigens in breast cancer

Benvenuto

Focaccetti²,

Izzi

et al. 2021

Seminars in Cancer Biology

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Computational Methods for Identification of T Cell Neoepitopes in Tumors

Cited by 10 publications

References 74 publications

Determinants for Neoantigen Identification

Determinants for Neoantigen Identification

TCR-like CARs and TCR-CARs targeting neoepitopes: an emerging potential

Tumor antigens heterogeneity and immune response-targeting neoantigens in breast cancer

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