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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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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Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL

Nature, Год журнала: 2022, Номер 609(7926), С. 369 - 374

Опубликована: Авг. 31, 2022

Abstract Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies 1–7 . However, CAR-T currently several limitations 8–12 Here we successfully developed a two-in-one approach to generate non-viral, gene-specific targeted cells through CRISPR–Cas9. Using the optimized protocol, demonstrated feasibility preclinical study by inserting an anti-CD19 CAR cassette into AAVS1 safe-harbour locus. Furthermore, innovative type of with PD1 integration was and showed superior ability eradicate tumour xenograft models. In adoptive for relapsed/refractory aggressive B non-Hodgkin lymphoma (ClinicalTrials.gov, NCT04213469 ), observed high rate (87.5%) complete remission durable responses without serious adverse events eight patients. Notably, these enhanced were effective even at low infusion dose percentage + cells. Single-cell analysis that electroporation method resulted memory T products, interference anti-tumour immune functions, further validating advantages -integrated Collectively, our results demonstrate safety efficacy integrated cells, thus providing technology therapy.

Язык: Английский

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Roles of tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for solid cancers

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Март 21, 2023

Abstract In recent years, tumor immunotherapy has made significant progress. However, immunotherapy, particularly immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors), benefits only a tiny proportion of patients in solid cancers. The microenvironment (TME) acts role immunotherapy. Studies reported that tumor-associated macrophages (TAMs), as one the main components TME, seriously affected therapeutic effect inhibitors. this review, we analyzed TAMs from epigenetic and single-cell perspectives introduced mechanisms anti-programmed death protein 1(anti-PD-1) therapy. addition, summarized combination regimens enhance efficacy elaborated on different Eventually, clinical value by influencing was discussed. These above are beneficial to elucidate poor tumors point view explore strategies improve its objective remission rate

Язык: Английский

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Breast cancer heterogeneity and its implication in personalized precision therapy

Experimental Hematology and Oncology, Год журнала: 2023, Номер 12(1)

Опубликована: Янв. 9, 2023

Abstract Breast cancer heterogeneity determines progression, treatment effects, and prognosis. However, the precise mechanism for this remains unknown owing to its complexity. Here, we summarize origins of breast influence on disease recurrence, therapeutic resistance. We review possible mechanisms research methods used analyze it. also highlight importance cell interactions heterogeneity, which can be further categorized into cooperative competitive interactions. Finally, provide new insights individual treatments based heterogeneity.

Язык: Английский

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Tumor organoids: applications in cancer modeling and potentials in precision medicine

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Май 12, 2022

Abstract Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity associated metastasis, relapse, and therapy resistance. These factors contribute to treatment failure an unfavorable prognosis. Personalized tumor models faithfully capturing the of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise powerful organoid technology generation vitro three-dimensional tissues that been shown more accurately recapitulate structures, specific functions, molecular characteristics, genomic alterations, expression profiles, microenvironment primary tumors. Tumoroids serve as important component pipeline discovery potential therapeutic targets identification novel compounds. In this review, we will summarize recent advances tumoroid cultures excellent tool accurate cancer modeling. Additionally, vascularization immune modeling based on also be described. Furthermore, great organoids predicting response, investigating resistance-related mechanisms, optimizing strategies, exploring therapies. addition, bottlenecks challenges current tumoroids discussed review.

Язык: Английский

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Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Окт. 8, 2022

Abstract The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, gene therapy products) have approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 these were identified cancer therapeutics cancer-related drugs, 120 them classified therapeutic for solid tumors according to their initial indications. These evolved from small molecules with broad-spectrum antitumor properties early stage monoclonal antibodies (mAbs) antibody‒drug conjugates (ADCs) more precise targeting effect during most recent decade. extended indications other malignancies, constituting treatment system monotherapy combined therapy. However, available targets are still mainly limited receptor tyrosine kinases (RTKs), restricting development drugs. In this review, summarized indications, characteristics, functions. Additionally, RTK-targeted therapies immune checkpoint-based immunotherapies also discussed. Our analysis existing challenges potential opportunities may advance tumor future.

Язык: Английский

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Emerging Sonodynamic Therapy‐Based Nanomedicines for Cancer Immunotherapy

Advanced Science, Год журнала: 2022, Номер 10(2)

Опубликована: Ноя. 27, 2022

Cancer immunotherapy effect can be greatly enhanced by other methods to induce immunogenic cell death (ICD), which has profoundly affected as a highly efficient paradigm. However, these treatments have significant limitations, either causing damage of the immune system or limited superficial tumors. Sonodynamic therapy (SDT) ICD promote without affecting because its excellent spatiotemporal selectivity and low side effects. Nevertheless, SDT is still reactive oxygen species yield complex tumor microenvironment. Recently, some emerging SDT-based nanomedicines made numerous attractive encouraging achievements in field cancer due high immunotherapeutic efficiency. this cross-cutting research far from being widely explored huge professional barriers. Herein, characteristics microenvironment mechanisms are firstly systematically summarized. Subsequently, therapeutic mechanism fully summarized, advantages limitations discussed. The representative advances for further highlighted. Finally, application prospects challenges future clinical translation

Язык: Английский

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Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Acta Pharmaceutica Sinica B, Год журнала: 2022, Номер 12(12), С. 4327 - 4347

Опубликована: Ноя. 4, 2022

Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies, on account of its good safety long-term memory ability. Discouragingly, low patient response rates potential immune-related side effects make it rather challenging to literally bring from bench bedside. However, become evident that, although immunosuppressive microenvironment (TME) plays a pivotal role in facilitating progression metastasis, also provides various targets for remodeling TME, which can consequently bolster effectiveness antitumor suppression. Additionally, particular characteristics turn, be exploited as avenues designing diverse precise targeting nanomedicines. In general, is urgent necessity deliver nanomedicines thus improving therapeutic outcomes clinical translation prospects immunotherapy. Herein, we will illustrate several formation mechanisms TME. More importantly, variety strategies concerning TME strengthening patients' immune systems, reviewed. Ultimately, discuss existing obstacles future perspectives development Hopefully, thriving bloom vibrancy further exploration comprehensive cancer treatment.

Язык: Английский

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Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1/PD-L1 blockade

Drug Resistance Updates, Год журнала: 2022, Номер 66, С. 100907 - 100907

Опубликована: Ноя. 30, 2022

Язык: Английский

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