Next-generation sequencing technologies accelerate advances in T-cell therapy for cancer

Yin, Qinan; Tang, Jiaxing; Zhu, Xuekai

doi:10.1093/bfgp/ely018

Cited by 7 publications

(6 citation statements)

References 97 publications

(134 reference statements)

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“…Results represent 1 of 2 independent experiments ◂ (NGS) have provided insights into the biology and mutational landscape of cancer. With the development of NGS, the WES of the tumour DNA in combination with RNA-Seq and in silico HLA-binding prediction has been used to identify nonsynonymous cancer mutations recognised by T cells (Yin et al 2019). Tumour neo-antigens can be predicted and identified according to the affinity analysis of peptides to MHC molecules or mass spectrometry analysis.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumour effect of neo-antigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer

Sun

Zhang

et al. 2021

J Cancer Res Clin Oncol

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Purpose Mutation-specific T-cell response to epithelial cancers and T-cell-based immunotherapy has been successfully used to treat several human solid cancers. We aimed to investigate the anti-tumour effect of neo-antigen-reactive T(NRT) cells induced by RNA mutanome vaccine, which may serve as a feasible and effective therapeutic approach for lung cancer. Methods We predicted candidate neo-antigens according to the mutant gene analysis by sequencing the mouse Lewis cells and C57BL/6 mouse tail tissue. RNA vaccine was prepared with the neo-antigens as the template. We assessed antitumor efficacy, cytokine secretion and pathological changes after adoptive transfer of NRT cells in vitro and vivo experiments. Results We identified 10 non-synonymous somatic mutations and successfully generated NRT cells. The percentage of T-cell activation proportion was increased from 0.072% in conventional T cells to 9.96% in NRT cells. Interferon-γ secretion augmented from 17.8 to 24.2% as well. As an in vivo model, adoptive NRT cell infusion could promote active T-cell infiltration into the tumour tissue and could delay tumour progression. Conclusion NRT cells induced by RNA mutanome vaccine exert a significant anti-tumour effect in mouse lung cancer, and adoptive NRT cell therapy might be considered a feasible, effective therapeutic approach for lung cancer.

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Section: Discussionmentioning

confidence: 99%

Anti-tumour effect of neo-antigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer

Sun

Zhang

et al. 2021

J Cancer Res Clin Oncol

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“…Nextgeneration sequencing technologies(NGS) have provided insights into the biology and mutational landscape of cancer. With the development of NGS, the WES of the tumour DNA in combination with RNA-Seq and in silico HLA-binding prediction has been used to identify nonsynonymous cancer mutations recognised by T cells (Yin, Tang, & Zhu, 2019). Tumour neoantigens can be predicted and identi ed according to the a nity analysis of peptides to MHC molecules or mass spectrometry analysis.…”

Section: Discussionmentioning

confidence: 99%

Antitumour effect of neoantigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer

Sun

Zhang

et al. 2021

Preprint

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Purpose Mutation-specific T-cell response to epithelial cancers and T-cell-based immunotherapy has been successfully used to treat several human solid cancers. We aimed to investigate the antitumour effect of neoantigen-reactive T(NRT) cells induced by RNA mutanome vaccine, which may serve as a feasible and effective therapeutic approach for lung cancer. Methods We predicted candidate neoantigens according to the mutant gene analysis by sequencing the mouse Lewis cells and C57BL/6 mouse tail tissue. RNA vaccine was prepared with the neoantigens as the template. We assessed antitumor efficacy, cytokine secretion and pathological changes after adoptive transfer of NRT cells in vitro and vivo experiments. Results We identified 10 nonsynonymous somatic mutations and successfully generated NRT cells. The percentage of T-cell activation proportion was increased from 0.072% in conventional T cells to 9.96% in NRT cells. Interferon-γ secretion augmented from 17.8–24.2% as well. As an in vivo model, adoptive NRT cell infusion could promote active T-cell infiltration into the tumour tissue and could delay tumour progression. Conclusions NRT cells induced by RNA mutanome vaccine exert a significant antitumour effect in mouse lung cancer, and adoptive NRT cell therapy might be considered a feasible, effective therapeutic approach for lung cancer.

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“…RNA sequencing (RNA‐seq) can be used to quantify gene expression, including the target antigen, at a genome‐wide level. NGS‐based approaches can overcome some of the limitations of traditional methods and provide a more comprehensive view of antigen expression dynamics 39 Imaging techniques : Multiplex immunofluorescence and mass cytometry (CyTOF) are advanced techniques that enable the simultaneous detection of multiple antigens within tissue samples 40,41 .…”

Section: Detection and Monitoring Of Antigen Lossmentioning

confidence: 99%

“…Next-generation sequencing (NGS) 38,39 Sensitivity: High Specificity: High •Provides a comprehensive view of gene expression, including antigen expression profiles.…”

mentioning

confidence: 99%

“…Next-generation sequencing (NGS): It can provide comprehensive genomic profiling, including assessment of antigen expression 38. RNA sequencing (RNA-seq) can be used to quantify gene expression, including the target antigen, at a genome-wide level.NGS-based approaches can overcome some of the limitations of traditional methods and provide a more comprehensive view of antigen expression dynamics 39. b.…”

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confidence: 99%

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Antigen loss following CAR‐T cell therapy: Mechanisms, implications, and potential solutions

Mishra,

Maiti,

Mohan

et al. 2023

European J of Haematology

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Chimeric Antigen Receptor T‐cell (CAR‐T cell) therapy has emerged as a groundbreaking immunotherapeutic approach for treating various hematological malignancies. CAR‐T cells are engineered to express synthetic receptors that target specific antigens on cancer cells, leading to their eradication. While the therapy has shown remarkable efficacy, a significant challenge that has been observed in 30%–70% of patients showing recurrent disease is antigen loss or downregulation. We searched PubMed/MEDLINE, EMBASE, and Google scholar for articles on antigen loss/escape following Chimeric antigen receptor T‐cell therapy in malignancies. Antigen loss refers to the loss or reduction in the expression of the target antigen on cancer cells, rendering CAR‐T cells ineffective. This phenomenon poses a significant clinical concern, as it can lead to disease relapse and limited treatment options. This review explores the mechanisms underlying antigen loss following CAR‐T cell therapy, its implications on treatment outcomes, and potential strategies to overcome the problem.

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Next-generation sequencing technologies accelerate advances in T-cell therapy for cancer

Cited by 7 publications

References 97 publications

Anti-tumour effect of neo-antigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer

Anti-tumour effect of neo-antigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer

Antitumour effect of neoantigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer

Antigen loss following CAR‐T cell therapy: Mechanisms, implications, and potential solutions

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