Artificial Polymerizations in Living Organisms for Biomedical Applications DOI
Yun Chen,

Brynne Shu Ni Tan,

Yu Cheng

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Abstract Within living organisms, numerous nanomachines are constantly involved in complex polymerization processes, generating a diverse array of biomacromolecules for maintaining biological activities. Transporting artificial polymerizations from lab settings into contexts has expanded opportunities understanding and managing events, creating novel cellular compartments, introducing new functionalities. This review summarizes the recent advancements polymerizations, including those responding to external stimuli, internal environmental factors, that polymerize spontaneously. More importantly, cutting‐edge biomedical application scenarios polymerization, notably safeguarding cells, modulating improving diagnostic performance, facilitating therapeutic efficacy highlighted. Finally, this outlines key challenges technological obstacles remain as well offers insights potential directions advancing their practical applications clinical trials.

Language: Английский

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy DOI Creative Commons
Matin Chehelgerdi,

Fereshteh Behdarvand Dehkordi,

Mohammad Chehelgerdi

et al.

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

Published: Nov. 28, 2023

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. formation is multifaceted process influenced by genetic, epigenetic, and environmental factors. offer distinctive platform investigating the origin cancer, paving way novel approaches to treatment, drug testing, tailored medical interventions. This review article will provide an overview science behind iPSCs, current limitations challenges iPSC-based therapy, ethical social implications, comparative analysis with other types also discuss applications tumorigenesis, future tumorigenesis highlight successful case studies utilizing research. conclusion summarize advancements made research importance continued investment iPSC unlock full potential these cells.

Language: Английский

Citations

68
Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies DOI Creative Commons
Yan-Ruide Li,

Ying Fang,

Zibai Lyu

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 2, 2023

Cancer stem cells (CSCs) have emerged as key contributors to tumor initiation, growth, and metastasis. In addition, CSCs play a significant role in inducing immune evasion, thereby compromising the effectiveness of cancer treatments. The reciprocal communication between microenvironment (TME) is observed, with TME providing supportive niche for CSC survival self-renewal, while CSCs, turn, influence polarization persistence TME, promoting an immunosuppressive state. Consequently, these interactions hinder efficacy current therapies, necessitating exploration novel therapeutic approaches modulate target CSCs. this review, we highlight intricate strategies employed by evade surveillance develop resistance therapies. Furthermore, examine dynamic interplay shedding light on how interaction impacts progression. Moreover, provide overview advanced that specifically which hold promise future clinical translational studies treatment.

Language: Английский

Citations

65
Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method DOI Creative Commons

Yan-Ruide Li,

Yang Zhou, Jiaji Yu

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Abstract Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using ‘off-the-shelf’ products, such as allogeneic CAR natural killer ( Allo CAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem progenitor into CAR-NKT cells, but the use of three-dimensional culture xenogeneic feeders precluded its clinical application. Here describe clinically guided method to differentiate expand IL-15-enhanced high yield purity. We generated targeting seven cancers and, multiple myeloma model, demonstrated their antitumor efficacy, expansion persistence. The also selectively depleted immunosuppressive tumor microenviroment antagonized immune evasion via triple CAR, TCR NK receptors. They exhibited stable hypoimmunogenic phenotype associated epigenetic signaling regulation did not induce detectable graft versus host disease or cytokine release syndrome. These properties support potential translation.

Language: Английский

Citations

22
Programmable synthetic receptors: the next-generation of cell and gene therapies DOI Creative Commons
Fei Teng,

Tongtong Cui,

Li Zhou

et al.

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

Published: Jan. 3, 2024

Abstract Cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat diseases. However, concerns over the safety efficacy require to be further addressed in order realize their full potential. Synthetic receptors, synthetic biology tool that can precisely control function therapeutic cells genetic modules, have been rapidly developed applied as powerful solution. Delicately designed engineered, they finetune activities, i.e., regulate production dosed, bioactive payloads by sensing processing user-defined signals or biomarkers. This review provides an overview diverse receptor systems being used reprogram wide applications biomedical research. With special focus on four at forefront, including chimeric antigen receptors (CARs) Notch (synNotch) we address generalized strategies design, construct improve receptors. Meanwhile, also highlight expanding landscape well current challenges clinical translation.

Language: Английский

Citations

20
A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy DOI Creative Commons
Na Li,

Shinan Geng,

Zhenzhen Dong

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 1, 2024

Abstract Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during previous ten years. However, its effectiveness treating solid tumors is still lacking, necessitating exploration alternative immunotherapies that can overcome significant challenges faced by current CAR-T cells. CAR-based immunotherapy against shows promise with emergence macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and ability to modify tumor microenvironment stimulate adaptive responses. This paper presents a thorough examination latest progress CAR-M therapy, covering both basic scientific studies clinical trials. study examines primary obstacles hindering realization complete potential as well strategies be employed these hurdles. With revolutionary technologies like situ genetic modification, synthetic biology techniques, biomaterial-supported gene transfer, provide wider array resources manipulating tumor-associated we suggest combining advanced methods will result creation new era therapy demonstrates improved efficacy, safety, availability. Graphical

Language: Английский

Citations

20
Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy DOI Creative Commons
Yan-Ruide Li,

Yang Zhou,

Jiaji Yu

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(6), P. 1849 - 1874

Published: April 6, 2024

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there a growing demand for off-the-shelf universal therapies. In this study, we have generated CAR-engineered NKT (

Language: Английский

Citations

18
Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update DOI Creative Commons
Agnete Kirkeby,

Heather Main,

Melissa Carpenter

et al.

Cell stem cell, Journal Year: 2025, Volume and Issue: 32(1), P. 10 - 37

Published: Jan. 1, 2025

Language: Английский

Citations

10
Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies DOI Creative Commons
Yan-Ruide Li,

Ying Fang,

Shaoqiang Niu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 1, 2025

Abstract Chimeric antigen receptor (CAR)-engineered T cell therapy holds promise for treating myeloid malignancies, but challenges remain in bone marrow (BM) infiltration and targeting BM-resident malignant cells. Current autologous CAR-T therapies also face manufacturing patient selection issues, underscoring the need off-the-shelf products. In this study, we characterize primary samples identify a unique therapeutic opportunity CAR-engineered invariant natural killer (CAR-NKT) Using stem gene engineering clinically guided culture method, generate allogeneic CD33-directed CAR-NKT cells with high yield, purity, robustness. preclinical mouse models, exhibit strong BM homing effectively target blast cells, including CD33-low/negative leukemia progenitor Furthermore, synergize hypomethylating agents, enhancing tumor-killing efficacy. These show minimal off-tumor toxicity, reduced graft-versus-host disease cytokine release syndrome risks, resistance to allorejection, highlighting their substantial potential malignancies.

Language: Английский

Citations

3
Boosting CAR-T cell therapy through vaccine synergy DOI Creative Commons
Yan-Ruide Li,

Zibai Lyu,

Xinyuan Shen

et al.

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematological cancers. However, achieving comparable success in solid tumors remains challenging. Factors contributing to these limitations include scarcity of tumor-specific antigens (TSAs), insufficient CAR-T infiltration, and immunosuppressive tumor microenvironment (TME). Vaccine-based strategies are emerging as potential approaches address challenges, enhancing expansion, persistence, antitumor efficacy. In this review, we explore diverse vaccine modalities, including mRNA, peptide, viral vector, dendritic (DC)-based vaccines, their roles augmenting responses. Special focus is given recent clinical advancements combining mRNA-based vaccines with genitourinary addition, discuss crucial considerations optimizing dosing, scheduling, delivery maximize synergy, aiming refine combination strategy improve efficacy safety.

Language: Английский

Citations

2
The future of affordable cancer immunotherapy DOI Creative Commons
Niels Schaft, Jan Dörrie, Gerold Schuler

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 6, 2023

The treatment of cancer was revolutionized within the last two decades by utilizing mechanism immune system against malignant tissue in so-called immunotherapy. Two main developments boosted immunotherapy: 1) use checkpoint inhibitors, which are characterized a relatively high response rate mainly solid tumors; however, at cost serious side effects, and 2) chimeric antigen receptor (CAR)-T cells, were shown to be very efficient hematologic malignancies, but failed show clinical effectiveness tumors until now. In addition, active immunization individual is emerging, first products have reached approval. These new options cost-intensive not financially compensated health insurance many countries. Hence, strategies must developed make immunotherapy affordable improve cost-benefit ratio. this review, we discuss following strategies: leverage antigenicity “cold tumors” with reagents, microbiome-based as markers or therapeutics, 3) apply measures that adoptive cell therapy (ACT) cheaper, e.g., off-the-shelf products, 4) immunotherapies offer cheaper platforms, such RNA- peptide-based vaccines shared common antigens instead highly personal antigens, 5) small set predictive biomarkers “sequence everything” approach, 6) explore immunohistochemistry may direct therapies.

Language: Английский

Citations

39