CD8+ T cell differentiation and dysfunction in cancer

Nature reviews. Immunology, Год журнала: 2021, Номер 22(4), С. 209 - 223

Опубликована: Июль 12, 2021

Язык: Английский

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Neoantigens: promising targets for cancer therapy

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Янв. 6, 2023

Abstract Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by cells as a result various tumor-specific alterations, such genomic mutation, dysregulated RNA splicing, disordered post-translational modification, integrated viral open reading frames. recognized non-self trigger an immune response that is not subject to central peripheral tolerance. The quick identification prediction neoantigens been made possible advanced next-generation sequencing bioinformatic technologies. Compared tumor-associated antigens, highly immunogenic provide emerging targets personalized serve prospective predictors survival prognosis checkpoint blockade responses. therapies will be aided understanding mechanism underlying neoantigen-induced anti-tumor streamlining process neoantigen-based immunotherapies. This review provides overview on characterization outlines clinical applications immunotherapeutic strategies based neoantigens. We also explore their current status, inherent challenges, translation potential.

Язык: Английский

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A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance

Nature Immunology, Год журнала: 2022, Номер 23(5), С. 660 - 670

Опубликована: Март 3, 2022

Язык: Английский

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The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Сен. 13, 2022

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, natural for PD-1, mainly in tumor Studies have indicated that PD-1 and PD-L1 are closely associated with progression human cancers promising biomarkers cancer therapy. Moreover, interaction one important mechanism by which tumors generate escape. This article provides review role PD-L1/PD-1, mechanisms response resistance, as well immune-related adverse events treatment anti-PD-1/PD-L1 immunotherapy cancers. we summarized large number clinical trials to successfully reveal PD-1/PD-L1 Immune-checkpoint inhibitors manifested therapeutic effects, been evaluated from different perspectives, including overall survival, objective effective rate medium progression-free survival. Finally, pointed out current problems faced its future prospects. Although widely used cancers, tough challenges still remain. Combination therapy predictive models based integrated biomarker determination theory may be directions application treating

Язык: Английский

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Dynamics and specificities of T cells in cancer immunotherapy

Nature reviews. Cancer, Год журнала: 2023, Номер 23(5), С. 295 - 316

Опубликована: Апрель 12, 2023

Язык: Английский

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Promises and challenges of adoptive T-cell therapies for solid tumours

British Journal of Cancer, Год журнала: 2021, Номер 124(11), С. 1759 - 1776

Опубликована: Март 29, 2021

Abstract Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous allogeneic transplant tumour-infiltrating lymphocytes genetically modified T cells expressing novel receptors chimeric antigen receptors, has shown promise in treatment cancer patients, durable responses some cases, cure. Technological advances genomics, computational biology, immunology cell manufacturing have brought aspiration individualised for closer reality. This era cell-based therapeutics challenges traditional standards therapeutic interventions provides opportunities paradigm shift our approach therapy. Invited speakers at 2020 symposium discussed three areas—cancer cell-therapy manufacturing—that are essential effective translation solid malignancies. Key been made understanding genetic intratumour heterogeneity, strategies accurately identify neoantigens, overcome exhaustion circumvent tumour immunosuppression after infusion being developed. Advances cell-manufacturing approaches that potential establish cell-therapies as credible options. face but hold great improving clinical outcomes tumours.

Язык: Английский

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TCR-engineered T cell therapy in solid tumors: State of the art and perspectives

Science Advances, Год журнала: 2023, Номер 9(7)

Опубликована: Фев. 15, 2023

T cell engineering has changed the landscape of cancer immunotherapy. Chimeric antigen receptor cells have demonstrated a remarkable efficacy in treatment B malignancies hematology. However, their clinical impact on solid tumors been modest so far. expressing an engineered (TCR-T cells) represent promising therapeutic alternative. The target repertoire is not limited to membrane proteins, and intrinsic features TCRs such as high sensitivity near-to-physiological signaling may improve tumor detection killing while improving persistence. In this review, we present results obtained with TCR-T targeting different families. We detail methods that developed identify optimize TCR candidate. also discuss challenges therapies, including toxicity assessment resistance mechanisms. Last, share some perspectives highlight future directions field.

Язык: Английский

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Therapeutic cancer vaccines: advancements, challenges and prospects

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 13, 2023

With the development and regulatory approval of immune checkpoint inhibitors adoptive cell therapies, cancer immunotherapy has undergone a profound transformation over past decades. Recently, therapeutic vaccines have shown promise by eliciting de novo T responses targeting tumor antigens, including tumor-associated antigens tumor-specific antigens. The objective was to amplify diversify intrinsic repertoire cells. However, complete realization these capabilities remains an ongoing pursuit. Therefore, we provide overview current landscape in this review. range antigen selection, delivery systems strategic nuances underlying effective presentation pioneered vaccine design. Furthermore, review addresses status clinical trials discusses their strategies, focusing on immunogenicity anti-tumor efficacy assessment. attempts toward developing not yielded breakthrough outcomes due significant challenges, microenvironment suppression, optimal candidate identification, response evaluation, manufacturing acceleration. field is poised overcome hurdles improve patient future acknowledging complexities persistently striving surmount inherent constraints.

Язык: Английский

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From bench to bedside: the history and progress of CAR T cell therapy

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 15, 2023

Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in cancer care since the approval of tisagenlecleucel by Food and Drug Administration 2017 for treatment pediatric young adult patients with relapsed or refractory acute lymphocytic leukemia. As April 2023, six CAR therapies have been approved, demonstrating unprecedented efficacy B-cell malignancies multiple myeloma. However, adverse events such as cytokine release syndrome immune effector cell-associated neurotoxicity pose significant challenges to therapy. The severity these correlates pretreatment tumor burden, where higher burden results more severe consequences. This observation is supported application CD19-targeted autoimmune diseases including systemic lupus erythematosus antisynthetase syndrome. These indicate that initiating early at low using debulking strategy prior infusion may reduce events. In addition, expensive has limited effectiveness against solid tumors. this article, we review critical steps led groundbreaking explore ongoing efforts overcome challenges. With promise effective safer development, are optimistic broader range will benefit from revolutionary foreseeable future.

Язык: Английский

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Engineering strategies to enhance oncolytic viruses in cancer immunotherapy

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Апрель 6, 2022

Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed. In addition to direct oncolysis, the essential attractive aspect of oncolytic virotherapy is based on intrinsic induction both innate adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered express regulators that enhance or restore antitumor immunity. Recently, combinations other immunotherapies, such checkpoint inhibitors (ICIs), chimeric antigen receptors (CARs), antigen-specific T-cell (TCRs) autologous tumor-infiltrating lymphocytes (TILs), led promising progress cancer treatment. This review summarizes mechanisms OVs, describes optimization strategies using armed effects immunity highlights rational immunotherapies recent preclinical clinical studies.

Язык: Английский

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