Screening and mechanistic study of natural compounds that enhance T cell anti-tumor effects post-heat treatment DOI Creative Commons

Zhaoyi Wang,

Zongli Diao, Yiyan Zhang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Introduction Following the approval of Chimeric Antigen Receptor T-cell Immunotherapy(CAR-T) in multiple countries, Food and Drug Administration (FDA) approved tumor-infiltrating lymphocytes (TILs) receptor-engineered T cells (TCR-T) treatments this year. The utilization adoptive immunotherapy tumor treatment has become increasingly prominent. Optimizing cytotoxic effects immune under vitro culture conditions represents a current hot research topic domain. Methods In experiment, we conducted heat on Jurkat-derived at 39°C. On basis, utilized nine distinct injectable solutions over 70 monomer components Traditional Chinese Medicine (TCM). Subsequently, co-cultured these treated Jurkat with K562-eGFP cells, co-culture process was monitored real-time using IncuCyte live-cell analysis system. Equally important, combined HiMAP high-throughput transcriptome sequencing, proteomics, metabolomics for in-depth examination. We screened compounds possessing anti-tumor properties thoroughly investigated their mechanisms action. Results Discussion findings indicated that heating augmented effect against malignant tumors, optimal achieved when were exposed to 39°C duration 24 hours(48% increase cell proliferation rate compared 37°C treatment). By triggering generation shock proteins facilitating mitochondrial energy supply, amplified functions cells. analyzing data, identified 3 more than 20 effective monomers capable further enhancing tumor-killing ability High-throughput transcriptomics studies disclosed combination thermotherapy TCM promoted proliferation, activation, thereby activating Regulation mitotic cycle exert effects. integration transcriptomic proteomic data demonstrated Shengmai Injection significantly enhances by down-regulating Apoptosis signaling pathways.

Language: Английский

Exploiting innate immunity for cancer immunotherapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

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

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

Citations

82
Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions DOI Creative Commons

Peilin Lu,

Dongxue Ruan,

Meiqi Huang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 1, 2024

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements potential therapeutic applications, focusing primarily on two areas: emerging cell-based therapies promising non-cell modalities. Within context cell therapy, discuss capacity overcome existing translational challenges faced by mainstream therapy paradigms, provide a detailed discussion advantages principal design considerations for boosting efficacy as well list specific examples different disease scenarios. We then explore drug delivery, physical intervention therapies, other areas (e.g., bioadhesives, artificial tissues, biosensors), emphasizing utility beyond mere delivery vehicles. Additionally, complement our latest progress clinical application outline future research directions, particularly terms integration with advanced biomanufacturing This review aims present comprehensive view critical insights into selection both tailored meet requirements diverse diseases situations.

Language: Английский

Citations

78
Revolutionizing cancer treatment: enhancing CAR-T cell therapy with CRISPR/Cas9 gene editing technology DOI Creative Commons

Ruiyu Tao,

Xiaopeng Han, Xue Bai

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 21, 2024

CAR-T cell therapy, a novel immunotherapy, has made significant breakthroughs in clinical practice, particularly treating B-cell-associated leukemia and lymphoma. However, it still faces challenges such as poor persistence, limited proliferation capacity, high manufacturing costs, suboptimal efficacy. CRISPR/Cas system, an efficient simple method for precise gene editing, offers new possibilities optimizing cells. It can increase the function of cells reduce costs. The combination CRISPR/Cas9 technology therapy may promote development this provide more effective personalized treatment cancer patients. Meanwhile, safety issues surrounding application require further research evaluation. Future should focus on improving accuracy to facilitate better therapy. This review focuses including eliminating inhibitory effect immune checkpoints, enhancing ability resist exhaustion, assisting construction universal cells, reducing costs security problems faced. objective is show revolutionary role researchers.

Language: Английский

Citations

28
CAR‑T cell therapy: A breakthrough in traditional cancer treatment strategies (Review) DOI Creative Commons

Dahua Sun,

Xiang Shi, Sanyan Li

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(3)

Published: Jan. 23, 2024

Chimeric antigen receptor (CAR)‑T cell therapy is an innovative approach to immune that works by modifying the T cells of a patient express CAR protein on their surface, and thus induce recognition destruction cancer cells. CAR‑T has shown some success in treating hematological tumors, but it still faces number challenges treatment solid such as selection, tolerability safety. In response these issues, studies continue improve design pursuit improved therapeutic efficacy future, expected become important treatment, may provide new ideas strategies for individualized immunotherapy. The present review provides comprehensive overview principles, clinical applications, therapy.

Language: Английский

Citations

17
CRISPR/Cas9: A Powerful Strategy to Improve CAR-T Cell Persistence DOI Open Access
Wei Wei, Zhi‐Nan Chen, Ke Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12317 - 12317

Published: Aug. 1, 2023

As an emerging treatment strategy for malignant tumors, chimeric antigen receptor T (CAR-T) cell therapy has been widely used in clinical practice, and its efficacy markedly improved the past decade. However, effect of CAR-T is not so satisfying, especially solid tumors. Even hematologic malignancies, a proportion patients eventually relapse after receiving infusions, owing to poor expansion persistence cells. Recently, CRISPR/Cas9 technology provided effective approach promoting proliferation cells body. This utilized generate memory phenotype, reduce exhaustion, screen new targets improve anti-tumor potential. In this review, we aim describe major causes limiting discuss application function. Finally, investigate trials CRISPR/Cas9-engineered cancer.

Language: Английский

Citations

38
New cell sources for CAR-based immunotherapy DOI Creative Commons
Marzieh Mazinani, Fatemeh Rahbarizadeh

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: May 6, 2023

Chimeric antigen receptor (CAR) T cell therapy, in which a patient's own lymphocytes are engineered to recognize and kill cancer cells, has achieved striking success some hematological malignancies preclinical clinical trials, resulting six FDA-approved CAR-T products currently available the market. Despite impressive outcomes, concerns about treatment failure associated with low efficacy or high cytotoxicity of cells remain. While main focus been on improving exploring alternative cellular sources for CAR generation garnered growing interest. In current review, we comprehensively evaluated other rather than conventional generation.

Language: Английский

Citations

25
The role of MSCs and CAR-MSCs in cellular immunotherapy DOI Creative Commons

Lun Yan,

Jing Li, Cheng Zhang

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 1, 2023

Abstract Chimeric antigen receptors (CARs) are widely used by T cells (CAR-T cells), natural killer dendritic and macrophages, they of great importance in cellular immunotherapy. However, the use CAR-related products faces several challenges, including poor persistence carrying CARs, cell dysfunction or exhaustion, relapse disease, immune effector cell-associated neurotoxicity syndrome, cytokine release low efficacy against solid tumors immunosuppression tumor microenvironment. Another important therapy regimen involves mesenchymal stem (MSCs). Recent studies have shown that MSCs can improve anticancer functions products. CAR-MSCs overcome flaws Thus, be as a biological vehicle for CARs. In this review, we first discuss characteristics immunomodulatory MSCs. Then, role source exosomes, MSC-derived exosomes their functions, is discussed. The products, product-derived effect on reviewed. Finally, CAR vehicles Graphical

Language: Английский

Citations

23
Enhancing cancer therapy: the integration of oncolytic virus therapy with diverse treatments DOI Creative Commons
Yan Zhuo, Zhengbo Zhang, Yanan Chen

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 11, 2024

Abstract As one of the significant challenges to human health, cancer has long been a focal point in medical treatment. With ongoing advancements field medicine, numerous methodologies for therapy have emerged, among which oncolytic virus gained considerable attention. However, viruses still exhibit limitations. Combining them with various therapies can further enhance efficacy treatment, offering renewed hope patients. In recent research, scientists recognized promising prospect amalgamating diverse treatments, potentially surmounting restrictions singular approaches. The central concept this combined revolves around leveraging incite localized tumor inflammation, augmenting immune response immunotherapeutic efficacy. Through approach, patient's system better recognize and eliminate cells, simultaneously reducing evasion mechanisms against system. This review delves deeply into latest research progress concerning integration treatments its role types therapy. We aim analyze mechanisms, advantages, potential challenges, future directions combination By extensively exploring field, we instill fight cancer.

Language: Английский

Citations

11
Exploring CAR-macrophages in non-tumor diseases: Therapeutic potential beyond cancer DOI Creative Commons

Yizhao Chen,

Qianling Xin,

Mengjuan Zhu

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, first approved CAR product, has demonstrated therapeutic potential treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach immune particularly solid highlighting feasibility using macrophages to eliminate pathogens abnormal cells.

Language: Английский

Citations

1
A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8+ T cell fitness in solid tumours DOI Creative Commons
Samantha Pretto, Qian Yu, Pierre Bourdely

et al.

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Reprogramming T cell metabolism can improve intratumoural fitness. By performing a CRISPR/Cas9 metabolic survey in CD8 + cells, we identified 83 targets and applied single-cell RNA sequencing to disclose transcriptome changes associated with each perturbation the context of pancreatic cancer. This revealed elongation very long-chain fatty acids protein 1 ( Elovl1 ) as target sustain effector functions memory phenotypes cells. Accordingly, inactivation adoptively transferred cells combined anti-PD-1 showed therapeutic efficacy resistant melanoma tumours. The accumulation saturated -deficient destabilized INSIG1, leading SREBP2 activation, increased plasma membrane cholesterol stronger receptor signalling. mitochondrial fitness acid oxidation, thus withstanding stress imposed by tumour microenvironment. Finally, ELOVL1 correlated response patients melanoma. Altogether, targeting synergizes promote effective responses.

Language: Английский

Citations

1