Harnessing Type II Cytokines to Reinvigorate Exhausted T Cells for Durable Cancer Immunotherapy DOI Creative Commons

Wenle Zhang,

Y. G. Wang,

Bin Li

et al.

Genomics Proteomics & Bioinformatics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

Count of references: 10Cancer immunotherapy has made significant strides in developing immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-based cellular therapies recent years.Despite these advancements, the immunosuppressive nature tumor microenvironment (TME) its metabolic complexity continue to present substantial challenges.Within this hostile environment, tumor-infiltrating T cells often experience severe functional impairment reduced cytotoxic potential.One main barriers effective long-lasting control is cell exhaustiona state characterized by diminished effector functions, impaired proliferation, sustained expression inhibitory receptors like PD-1, TIM-3 LAG-3.Although CAR-T therapy revolutionized treatment hematological malignancies, relapse was constantly reported limited efficacy observed treating solid tumors, largely due TME rapid onset exhaustion.To better understand mechanisms behind responses, a large-scale single-cell multi-omics study profiled over one million pre-infusion CAR collected from 82 acute lymphoblastic leukemia patients, with clinical follow-up extending up 10 years [1].The analysis highlighted that elevated type II cytokine activity infusion products linked patients maintaining 8-year remission.At chromatin level, higher increased accessibility found at loci GATA3, while IFNG, STAT1, STAT4 TBX21 showed negligible differences.Remarkably, also identified small

Language: Английский

Reinventing type 2 immunity in cancer DOI
Marek Wagner, Hiroyoshi Nishikawa, Shigeo Koyasu

et al.

Nature, Journal Year: 2025, Volume and Issue: 637(8045), P. 296 - 303

Published: Jan. 8, 2025

Language: Английский

Citations

3
Comparative analysis and process optimization for manufacturing CAR-T using the PiggyBac system derived from cryopreserved versus fresh PBMCs DOI Creative Commons

Zenghui Xu,

Ruyue Wang, Yuanjian Xu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 11, 2025

Abstract Chimeric antigen receptor T (CAR-T) therapy holds promise for cancer treatment but faces challenges with using fresh patient cells, including manufacturing failures and logistical hurdles. Cryopreserved peripheral blood mononuclear cells (PBMCs) offer a potential solution, while lentiviral processes have been reported generating CAR-T from these few studies demonstrated successful PiggyBac electroporation methods. Therefore, the objectives of our study were twofold: Firstly, to conduct comparative on cryopreserved PBMCs, their respective preparations CAR-T. Secondly, establish preparation process PBMCs through optimization. The results revealed that long-term frozen viability in relatively stable manner. generated exhibited comparable expansion potential, cell phenotype, differentiation profiles, exhaustion markers, cytotoxicity against human ovarian line (SKOV-3) those derived PBMCs. Moreover, optimization, we further enhanced proliferation toxicity This approach has revolutionize production model by utilizing healthy donor instead cells. shift could mitigate issues affecting efficacy, such as suboptimal condition following illness or delays preparation.

Language: Английский

Citations

0
Targeting γc family cytokines with biologics: current status and future prospects DOI Creative Commons
Fabian Bick, Christophe Blanchetot, Bart N. Lambrecht

et al.

mAbs, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 18, 2025

Over the recent decades market potential of biologics has substantially expanded, and many top-selling drugs worldwide are now monoclonal antibodies or antibody-like molecules. The common gamma chain (γc) cytokines, Interleukin (IL-)2, IL-4, IL-7, IL-9, IL-15, IL-21, play pivotal roles in regulating immune responses, from innate to adaptive immunity. Dysregulation cell signaling by these cytokines is strongly associated with a range immunological disorders, which includes cancer as well autoimmune inflammatory diseases. Given essential role γc maintaining homeostasis, development therapeutic interventions targeting molecules poses unique challenges. Here, we provide an overview current either single multiple their respective receptor subunits across spectrum diseases, primarily focusing on antibodies, constructs, antibody-cytokine fusions. We summarize currently clinical trials, highlighting how they may offer advantages over existing therapies standard care, discuss advances this field. Finally, explore future directions novel intervention strategies cytokine family.

Language: Английский

Citations

0
Multiomics with Evolutionary Computation to Identify Molecular and Module Biomarkers for Early Diagnosis and Treatment of Complex Disease DOI Open Access
Han Cheng,

Mengyu Liang,

Yiwen Gao

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(3), P. 244 - 244

Published: Feb. 20, 2025

It is important to identify disease biomarkers (DBs) for early diagnosis and treatment of complex diseases in personalized medicine. However, existing methods integrating intelligence technologies multiomics predict key are limited by the dynamic characteristics omics data, making it difficult meet high-precision requirements biomarker characterization large dimensions. This study reviewed current analysis evolutionary computation (EC) considering essential DB identification problems advantages EC, aiming explore multiomics. In this study, EC-based strategies were summarized as algorithms, swarm other EC molecular module identification, respectively. Finally, we pointed out challenges research future directions. can enrich application theory promote interdisciplinary integration between bioinformatics.

Language: Английский

Citations

0
Precise CAR-T-cell Therapy Targeting Non-Cancerous Diseases: Advances in Precision Medicine and Bioengineering DOI Creative Commons
Chaojie Zhu, Fangzhou Wang, Zesheng Cheng

et al.

Precision medicine and engineering., Journal Year: 2025, Volume and Issue: unknown, P. 100024 - 100024

Published: March 1, 2025

Language: Английский

Citations

0
ETS-1 in tumor immunology: implications for novel anti-cancer strategies DOI Creative Commons

Siyu Wang,

Lei Wan, Xiao-Jun Zhang

et al.

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

Published: March 20, 2025

ETS-1, a key member of the Erythroblast Transformation-Specific (ETS) transcription factor family, plays an important role in cell biology and medical research due to its wide expression profile strong transcriptional regulation ability. It regulates fundamental biological processes, including proliferation, differentiation, apoptosis, is involved tumorigenesis metastasis, promoting malignant behaviors such as angiogenesis, matrix degradation, migration. Given association between ETS-1 overexpression aggressive characteristics multiple malignancies, it represents promising therapeutic target cancer treatment. This study aims systematically analyze within tumor immune microenvironment, elucidating mechanisms initiation, progression, metastasis. also investigates differential across tissues adjacent normal tissues, exploring potential molecular marker for diagnosis prognosis.

Language: Английский

Citations

0
Progress and challenges in developing allogeneic cell therapies DOI Creative Commons
T. Deuse, Sonja Schrepfer

Cell stem cell, Journal Year: 2025, Volume and Issue: 32(4), P. 513 - 528

Published: April 1, 2025

The new era of cell therapeutics has started with autologous products to avoid immune rejection. However, derived from allogeneic cells could be scaled and made available for a much larger patient population if rejection reliably overcome. In this review, we outline gene engineering concepts aimed at generating immune-evasive cells. First, summarize the current state therapies, second, compile still limited data replacement therapies. We emphasize advances in fast-developing field provide an optimistic outlook future

Language: Английский

Citations

0
CAR-T therapy in solid tumors DOI
Bing Du, Juliang Qin,

Boxu Lin

et al.

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(4), P. 665 - 679

Published: April 1, 2025

Language: Английский

Citations

0
New horizons at the interface of artificial intelligence and translational cancer research DOI
Josephine Yates, Eliezer M. Van Allen

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(4), P. 708 - 727

Published: April 1, 2025

Language: Английский

Citations

0
Depletion of CD8+ CAR T-cells leads to superior anti-tumor efficacy of pure CD4+ CAR T-cells against Acute Leukemias DOI
Tim Sauer, Qian Chen, Hao Yao

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract Chimeric antigen receptor T-cell (CART) therapy has shown impressive therapeutic efficacy in several hematologic malignancies, however primary or secondary treatment failure remains a significant challenge driving translational research to improve the functionality of CARTs. Here, we show optimal composition CARTs targeting acute leukemias with respect content CD4+ and CD8+ T-cells. Our analysis demonstrated that pure exhibited superior antitumor activity proliferative capacity vitro vivo compared CD8+-containing CART products. Furthermore, secretome CARTs, enriched for Th1 Th2 cytokines, was more potent stimulating anti-leukemic Mechanistically, found interaction induces apoptosis leading their impaired functionality. findings demonstrate persistence against warranting further exploration potential within early phase clinical trials.

Language: Английский

Citations

0