Accelerating therapeutic protein design with computational approaches toward the clinical stage DOI Creative Commons
Zhidong Chen, Xinpei Wang, Xu Chen

и другие.

Computational and Structural Biotechnology Journal, Год журнала: 2023, Номер 21, С. 2909 - 2926

Опубликована: Янв. 1, 2023

Therapeutic protein, represented by antibodies, is of increasing interest in human medicine. However, clinical translation therapeutic protein still largely hindered different aspects developability, including affinity and selectivity, stability aggregation prevention, solubility viscosity reduction, deimmunization. Conventional optimization the developability with widely used methods, like display technologies library screening approaches, a time cost-intensive endeavor, efficiency finding suitable solutions not enough to meet needs. In recent years, accelerated advancement computational methodologies has ushered transformative era field design. Owing their remarkable capabilities feature extraction modeling, integration cutting-edge strategies conventional techniques presents promising avenue accelerate progression design toward implementation. Here, we compared differences between small molecules provided an overview approaches applicable or several issues.

Язык: Английский

Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways DOI Creative Commons
Zhi Zhu, A. J. Robert McGray, Weijian Jiang

и другие.

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Окт. 11, 2022

Oncolytic viruses (OVs) represent a new class of multi-modal immunotherapies for cancer, with OV-elicited antitumor immunity being key to their overall therapeutic efficacy. Currently, the clinical effectiveness OV as monotherapy remains limited, and thus investigators have been exploring various combinations other anti-cancer agents demonstrated improved As cancer cells evolved alter signaling pathways enhanced cell proliferation, progression metastasis, these cellular molecular changes offer promising targets rational therapy design. In this regard, molecules in relevant or/and immune cells, such EGFR-KRAS (e.g., KRASG12C), PI3K-AKT-mTOR, ERK-MEK, JAK-STAT, p53, PD-1-PD-L1, epigenetic, or histone deacetylases, cGAS-STING) are currently under investigation potential synergize modulate milieu tumor microenvironment (TME), thereby improving sustaining immunity. many small molecule modulators developed shown strong potential, here we review findings related both OV-mediated immunotherapy utility immuno-oncology. Then, focus on discussion rationales strategies combining selected targeting TME enhance Finally, provide perspectives viewpoints application novel experimental systems technologies that can propel exciting branch medicine into bright future.

Язык: Английский

Процитировано

61
Nano-immunotherapy: overcoming delivery challenge of immune checkpoint therapy DOI Creative Commons
Seyed Hossein Kiaie,

Hossein Salehi‐Shadkami,

Mohammad‐Javad Sanaei

и другие.

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Сен. 21, 2023

Abstract Immune checkpoint (ICP) molecules expressed on tumor cells can suppress immune responses against tumors. ICP therapy promotes anti-tumor by targeting inhibitory and stimulatory pathways of like T dendritic (DC). The investigation into the combination therapies through novel inhibitors (ICIs) has been limited due to immune-related adverse events (irAEs), low response rate, lack optimal strategy for combinatorial cancer immunotherapy (IMT). Nanoparticles (NPs) have emerged as powerful tools promote multidisciplinary cooperation. feasibility efficacy targeted delivery ICIs using NPs overcome primary barrier, improve therapeutic efficacy, provide a rationale more clinical investigations. Likewise, conjugate or encapsulate ICIs, including antibodies, RNAs, small molecule inhibitors. Therefore, combining drug system (DDS) with could profitable immunotherapeutic treatment. This article reviews significant controlled DDS current data from pre-clinical trials mono- IMT limitations. Graphical

Язык: Английский

Процитировано

37
Uncovering the specificity and predictability of tryptophan metabolism in lactic acid bacteria with genomics and metabolomics DOI Creative Commons

Tong Pan,

Zhangming Pei, Zhifeng Fang

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2023, Номер 13

Опубликована: Март 13, 2023

Tryptophan is metabolized by microorganisms into various indole derivatives that have been proven to alleviate diseases and promote human health. Lactic acid bacteria (LAB) are a broad microbial concept, some of which developed as probiotics. However, the capacity most LAB metabolize tryptophan unknown. In this study, aim reveal rule metabolism in multi-omics. The findings showed were rich genes for catabolism multiple shared among species. Although number their homologous sequences was different, they could still form same metabolic enzyme system. metabolomic analysis revealed capable producing variety metabolites. Strains belonging species can produce metabolites similar yields. A few strains strain-specificity production indole-3-lactic (ILA), indole-3-acetic acid, 3-indolealdehyde (IAld). genotype-phenotype association analysis, found be highly consistent with outcomes gene prediction, particularly ILA, indole-3-propionic indole-3-pyruvic acid. overall prediction accuracy more than 87% on average, indicated predictability LAB. Additionally, influenced concentration levels ILA IAld significantly correlated numbers aromatic amino aminotransferase amidase, respectively. unique indolelactate dehydrogenase Ligilactobacillus salivarius primary factor contributing its large ILA. summary, we demonstrated distribution level explored correlation between phenotypes. specificity proven. These results provide novel genomic method discovery potential offer experimental data probiotics specific

Язык: Английский

Процитировано

34
A scientometrics and visualization analysis of oxidative stress modulator Nrf2 in cancer profiles its characteristics and reveals its association with immune response DOI Creative Commons
Song‐Bin Guo, Sheng Du,

Ke-Yu Cai

и другие.

Heliyon, Год журнала: 2023, Номер 9(6), С. e17075 - e17075

Опубликована: Июнь 1, 2023

Nrf2, an essential and fascinating transcription factor, enjoys a dual property in the occurrence development of inflammation cancer. For over two decades, numerous studies regarding Nrf2 cancer have been reported, whereas there is still lack scientometrics visualization analysis Hence, scientometric study oxidative stress modulator was implemented.After quality screening, we defined 7168 relevant from 2000 to 2021. CiteSpace, VOSviewer, R software, GraphPad Prism were used for following analysis, including field profiles, research hotspots, future predictions.The total number publications citations are 1058 54,690, respectively. After polynomial fitting curve prediction functions annual publication (y = 3.3909x2 - 13585x + 1 E+07) citation (185.45x2 743669x 7 E+08) generated. found that Biochemistry Molecular Biology correlates with highly, Free Radical Medicine good choice submitting Nrf2-related manuscripts. The current hotspots mainly focus on therapy its cellular molecular mechanisms. "antioxidant response element (87.5)", "gene expression (43.98)", responsive (21.14)", "chemoprevention (20.05)", "carcinogenesis (19.2)", "cancer chemoprevention (18.45)", "free radical (17.15)", "response (14.17)", "chemopreventive agent (14.04)" important study. In addition, "glutathione-S-transferase (47)", "keap1 (15.39)", "heme oxygenase gene (24.35)" cell fate More interestingly, by performing "InfoMap" algorithm, thematic map showed "immune response" but not well developed, indicating it deserves further exploration.This revealed directions research, our findings will offer vigorous roadmap this field.

Язык: Английский

Процитировано

28
An in-situ peptide-antibody self-assembly to block CD47 and CD24 signaling enhances macrophage-mediated phagocytosis and anti-tumor immune responses DOI Creative Commons

Weiqi Zhang,

Yinghua Zeng,

Qiuqun Xiao

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 6, 2024

Abstract Targeted immunomodulation for reactivating innate cells, especially macrophages, holds great promise to complement current adaptive immunotherapy. Nevertheless, there is still a lack of high-performance therapeutics blocking macrophage phagocytosis checkpoint inhibitors in solid tumors. Herein, peptide-antibody combo-supramolecular situ assembled CD47 and CD24 bi-target inhibitor (PAC-SABI) described, which undergoes biomimetic surface propagation on cancer cell membranes through ligand-receptor binding enzyme-triggered reactions. By simultaneously signaling, PAC-SABI enhances the phagocytic ability macrophages vitro vivo, promoting anti-tumor responses breast pancreatic mouse models. Moreover, building foundation PAC-SABI-induced repolarization increased CD8 + T tumor infiltration, sequential anti-PD-1 therapy further suppresses 4T1 progression, prolonging survival rate. The vivo construction PAC-SABI-based nano-architectonics provides an efficient platform bridging immunity maximize therapeutic potency.

Язык: Английский

Процитировано

15
Targets of tumor microenvironment for potential drug development DOI Creative Commons
Ling Zhang, Ziruoyu Wang,

Kailu Liu

и другие.

MedComm – Oncology, Год журнала: 2024, Номер 3(1)

Опубликована: Март 1, 2024

Abstract The tumor microenvironment (TME) is the ecosystem surrounding a tumor, which usually consists of nontumoral cells or components, and molecules they produce release. frequent continuous interplay between TME strongly affects development, disease progression, metastasis, responses to therapeutic interventions. As hub potential targets, has gained appreciable momentum in cancer research. Here we systematically review progress targeting as strategy develop novel antitumor drugs from immunological, stromal extracellular matrix components TME, shedding light on its complex synergies with cells. This exploration highlights transformative these elements hold refining treatment approaches. thorough examination not only accentuates TME's multifaceted nature but also positions it formidable avenue for propelling forward paradigms therapy. aims foster deeper understanding role oncogenesis exploitation advancing targeted, efficacious treatments, marking significant stride realm

Язык: Английский

Процитировано

11
Eosinophil‐Activating Semiconducting Polymer Nanoparticles for Cancer Photo‐Immunotherapy DOI
Chi Zhang, Jingsheng Huang,

Mengke Xu

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(30)

Опубликована: Май 3, 2024

Eosinophils are important immune effector cells that affect T cell-mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted outcome cancer immunotherapies. We herein report an eosinophil-activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, reinvigorate T-cell immunity for activated photo-immunotherapy. SPNe comprises amphiphilic a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via

Язык: Английский

Процитировано

11
Small-molecule-based targeted therapy in liver cancer DOI
Ming Yue, Yanqiu Gong,

Xuewen Fu

и другие.

Molecular Therapy, Год журнала: 2024, Номер 32(10), С. 3260 - 3287

Опубликована: Авг. 8, 2024

Язык: Английский

Процитировано

11
LRP1 induces anti-PD-1 resistance by modulating the DLL4-NOTCH2-CCL2 axis and redirecting M2-like macrophage polarisation in bladder cancer DOI
Hansen Lin, Liangmin Fu, Xinwei Zhou

и другие.

Cancer Letters, Год журнала: 2024, Номер 593, С. 216807 - 216807

Опубликована: Март 8, 2024

Язык: Английский

Процитировано

10
Current strategies for targeting HPK1 in cancer and the barriers to preclinical progress DOI
Hui Chen,

Xiangna Guan,

Chi He

и другие.

Expert Opinion on Therapeutic Targets, Год журнала: 2024, Номер 28(4), С. 237 - 250

Опубликована: Апрель 2, 2024

Hematopoietic progenitor kinase 1 (HPK1), a 97-kDa serine/threonine Ste20-related protein kinase, functions as an intracellular negative regulator, primarily in hematopoietic lineage cells, where it regulates T B dendritic and other immune cells. Loss of HPK1 activity results exacerbated cytokine secretion, enhanced cell signaling, improved viral clearance, thus increased restraint tumor growth. These findings highlight promising target for immuno-oncology treatments, culminating the advancement candidate compounds targeting to clinical trials by several biotech enterprises.

Язык: Английский

Процитировано

10