Clinical implications of T cell exhaustion for cancer immunotherapy

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(12), P. 775 - 790

Published: Oct. 10, 2022

Language: Английский

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Natural killer cells in antitumour adoptive cell immunotherapy

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(10), P. 557 - 575

Published: July 25, 2022

Language: Английский

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Applications of single-cell RNA sequencing in drug discovery and development

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(6), P. 496 - 520

Published: April 28, 2023

Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery development. New opportunities emerging in target identification owing to improved disease understanding through cell subtyping, highly multiplexed functional genomics screens incorporating scRNA-seq enhancing credentialling prioritization. ScRNA-seq is also aiding selection relevant preclinical models providing new insights into mechanisms action. In clinical development, can inform decision-making via biomarker for patient stratification more precise monitoring response progression. Here, we illustrate how methods being applied key steps discuss ongoing challenges their implementation pharmaceutical industry. There have been significant recent advances development remarkable Ferran colleagues primarily pipeline, from decision-making. Ongoing potential future directions discussed.

Language: Английский

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Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens

Science, Journal Year: 2023, Volume and Issue: 380(6646)

Published: May 4, 2023

Most variants associated with complex traits and diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome unknown effects. Using ancestrally diverse, biobank-scale GWAS data, massively parallel CRISPR screens, single-cell transcriptomic proteomic sequencing, we discovered 124

Language: Английский

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Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: June 20, 2022

Breast cancer is the most commonly diagnosed (estimated 2.3 million new cases in 2020) and leading cause of death 685,000 deaths women globally. cancers have been categorized into four major molecular subtypes based on immunohistochemistry (IHC) expression classic hormone growth factor receptors including estrogen receptor (ER), progesterone (PR), human epidermal 2 (HER2), as well a proliferation marker Ki-67 protein expression. Triple-negative breast (TNBC), subtype lacking ER, PR, HER2 expression, associated with high metastatic potential poor prognosis. TNBC accounts for approximately only 15%-20% diagnoses; it responsible cancer-related due to lack targeted treatment options this patient population, currently, systemic chemotherapy, radiation, surgical excision remain modalities these patients TNBC. Although general do not robust response immunotherapy, subset has demonstrated tumor mutation burden tumor-infiltrating lymphocytes, resembling features observed melanoma or lung cancers, which can benefit from immune checkpoint inhibitors (ICIs). Therefore, immunogenic nature aggressive disease presented an opportunity development TNBC-targeting immunotherapies. The recent US Food Drug Administration approval atezolizumab combination chemotherapeutic agent nab-paclitaxel PD-L1-positive unresectable, locally advanced, led era immunotherapy treatment. In addition, becomes active research area, both biology field oncology field. review, we will extend our coverage discoveries preclinical early results clinical trials molecule-based therapy cytokines, monoclonal antibodies, antibody-drug conjugates, bi-specific tri-specific ICIs, neoantigen vaccines; oncolytic virus-based therapies adoptive cell transfer-based TIL, chimeric antigen receptor-T (CAR-T), CAR-NK, CAR-M, T-cell receptor-T. end, list series challenges opportunities prospectively reveal novel technologies such high-throughput single-cell sequencing CRISPR gene editing-based screening generate knowledges immunotherapy.

Language: Английский

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Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 16, 2023

Abstract The incidence and mortality of cancer are the major health issue worldwide. Apart from treatments developed to date, unsatisfactory therapeutic effects cancers have not been addressed by broadening toolbox. advent immunotherapy has ushered in a new era solid tumors, but remains limited requires breaking adverse effects. Meanwhile, development advanced technologies can be further boosted gene analysis manipulation at molecular level. cutting-edge genome editing technology, especially clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), demonstrated its potential break limits cancers. In this review, mechanism CRISPR-Cas9-mediated powerful CRISPR toolbox introduced. Furthermore, we focus on reviewing impact CRISPR-induced double-strand breaks (DSBs) (knockout or knockin). Finally, discuss CRISPR-Cas9-based genome-wide screening for target identification, emphasis spatial genomics, present comprehensive application challenges basic research, translational medicine clinics CRISPR-Cas9.

Language: Английский

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Stem-like exhausted and memory CD8+ T cells in cancer

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(11), P. 780 - 798

Published: Oct. 11, 2023

Language: Английский

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Hallmarks of CD8+ T cell dysfunction are established within hours of tumor antigen encounter before cell division

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(9), P. 1527 - 1539

Published: Aug. 3, 2023

Language: Английский

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CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(10), P. 1089 - 1108

Published: Aug. 12, 2024

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.

Language: Английский

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Naturally occurring T cell mutations enhance engineered T cell therapies

Nature, Journal Year: 2024, Volume and Issue: 626(7999), P. 626 - 634

Published: Feb. 7, 2024

Language: Английский

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