Monovalent Anti-CD3 Antibodies Effectively Eliminate the TCR-Positive Fraction of TCR-Deleted Allogeneic CAR-T Cells to Prevent GVHD DOI Open Access
Ji Hwan Kim, Hyori Kim,

A-Neum Lee

et al.

Immune Network, Journal Year: 2024, Volume and Issue: 24(6)

Published: Jan. 1, 2024

Chimeric antigen receptor-transduced T (CAR-T) cell therapy is an effective against advanced hematological tumors. However, the use of autologous cells limits its timely and universal generation. Allogeneic CAR-T may be a good alternative as ready-to-use therapeutic. Graft-versus-host disease (GVHD) obstacle for allogeneic cells, but can prevented by TCR deletion through genome editing. remaining TCR-positive must eliminated costly, large-scale magnetic separation. Therefore, method removing needed. In this study, we found that monovalent anti-CD3 Abs such Fab single-chain variable fragment (scFv), not whole IgG, induce apoptosis

Language: Английский

Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met? DOI Creative Commons
Caroline Lonez, Eytan Breman

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 146 - 146

Published: Jan. 12, 2024

This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this other malignancies and broader patient populations. However, several limitations remain, including those associated the time-consuming highly personalized manufacturing of autologous CAR-Ts. Technologies establish "off-the-shelf" allogeneic CAR-Ts low alloreactivity currently developed, strong focus on gene-editing technologies. Although these technologies have many advantages, they also limitations, double-strand breaks in DNA safety risks as well lack modulation. As an alternative, non-gene-editing provide interesting approach support development future, possibilities fine-tuning gene expression easy development. Here, we will review different ways can be manufactured discuss which used. The biggest hurdles successful summarized, finally, overview current clinical evidence comparison its counterpart given.

Language: Английский

Citations

21
Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology DOI Creative Commons

Emile M. Youssef,

Brandon Fletcher,

Dannelle Palmer

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 13, 2025

Gene therapy has long been a cornerstone in the treatment of rare diseases and genetic disorders, offering targeted solutions to conditions once considered untreatable. As field advances, its transformative potential is now expanding into oncology, where personalized therapies address immune-related complexities cancer. This review highlights innovative therapeutic strategies, including gene replacement, silencing, oncolytic virotherapy, CAR-T cell therapy, CRISPR-Cas9 editing, with focus on their application both hematologic malignancies solid tumors. CRISPR-Cas9, revolutionary tool precision medicine, enables precise editing cancer-driving mutations, enhancing immune responses disrupting tumor growth mechanisms. Additionally, emerging approaches target ferroptosis—a regulated, iron-dependent form death—offering new possibilities for selectively inducing death resistant cancers. Despite significant breakthroughs, challenges such as heterogeneity, evasion, immunosuppressive microenvironment (TME) remain. To overcome these barriers, novel like dual-targeting, armored cells, combination checkpoint inhibitors ferroptosis inducers are being explored. rise allogeneic “off-the-shelf” offers scalable more accessible options. The regulatory landscape evolving accommodate advancements, frameworks RMAT (Regenerative Medicine Advanced Therapy) U.S. ATMP (Advanced Therapy Medicinal Products) Europe fast-tracking approval therapies. However, ethical considerations surrounding CRISPR-based editing—such off-target effects, germline ensuring equitable access—remain at forefront, requiring ongoing oversight. Advances non-viral delivery systems, lipid nanoparticles (LNPs) exosomes, improving safety efficacy By integrating innovations addressing concerns, poised revolutionize cancer treatment, providing durable, effective,

Language: Английский

Citations

3
Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy DOI Creative Commons

Fatemeh Dehghan,

Yekta Metanat,

Mandana Askarizadeh

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 11, 2025

Currently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy solid tumors, lethal adverse effects, high cost of autologous products, and the risk GvHD in allogeneic settings. As a potential alternative, CAR-NK can overcome most limitations provide off-the-shelf, safer, more affordable product. Although published results from preclinical clinical studies cells are promising, bottlenecks must be unlocked to maximize effectiveness therapy. These include vivo persistence, trafficking into tumor sites, modest sensitivity immunosuppressive microenvironment. In recent years, advances gene manipulation tools strategies have laid groundwork current This review will introduce existing discuss their advantages disadvantages. We also explore how these enhance therapy’s safety efficacy.

Language: Английский

Citations

3
The clinical landscape of CAR NK cells DOI Creative Commons

Lasse Vedel Jørgensen,

Emil Birch Christensen, Mike Bogetofte Barnkob

et al.

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 27, 2025

Abstract Chimeric antigen receptor (CAR) NK cell therapy has emerged as a promising alternative to CAR T therapy, offering significant advantages in terms of safety and versatility. Here we explore the current clinical landscape cells, their application hematologic malignancies solid cancers, well potential for treating autoimmune disorders. Our analysis draws from data collected 120 trials focused on presents insights into demographics characteristics these studies. We further outline specific targets diseases under investigation, along with major sources, genetic modifications, combination strategies, preconditioning- dosing regimens, manufacturing strategies being utilized. Initial results 16 demonstrate efficacy particularly B malignancies, where response rates are comparable those seen cells but lower severe adverse effects, such cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), graft-versus-host disease (GvHD). However, challenges remain tumor applications, only modest been observed date. reveals that research is increasingly enhancing persistence, broadening therapeutic targets, refining processes improve accessibility scalability. With recent advancements engineering increased predicted become an integral component next-generation immunotherapies, not cancer potentially immune-mediated well.

Language: Английский

Citations

2
Microfluidic technologies for enhancing the potency, predictability and affordability of adoptive cell therapies DOI
Zongjie Wang, Shana O. Kelley

Nature Biomedical Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Language: Английский

Citations

1
Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation DOI Open Access
Na Kyung Lee, Jong Wook Chang

Annals of Laboratory Medicine, Journal Year: 2024, Volume and Issue: 44(4), P. 314 - 323

Published: Feb. 16, 2024

The safety and efficacy of both cell gene therapies have been demonstrated in numerous preclinical clinical trials.Chimeric antigen receptor T (CAR-T) therapy, which leverages the technologies therapies, has also shown great promise for treating various cancers.Advancements pertinent fields highlighted challenges faced while manufacturing therapy products.Potential problems obstacles must be addressed to ease translation individual therapies.Literature reviews representative cell-based, gene-based, cell-based with regard their general processes, during manufacturing, QC specifications are limited.We review processes including those involving mesenchymal stem cells, viral vectors, CAR-T cells.The complexities associated subsequent QC/validation may present that could impede progression products.This article addresses these potential challenges.Further, we discuss use model its impact on therapy.

Language: Английский

Citations

9
Neuroblastoma: an ongoing cold front for cancer immunotherapy DOI Creative Commons
Paul Kennedy,

Demetra Zannoupa,

Meong Hi Son

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(11), P. e007798 - e007798

Published: Nov. 1, 2023

Neuroblastoma is the most frequent extracranial childhood tumour but effective treatment with current immunotherapies challenging due to its immunosuppressive microenvironment. Efforts date have focused on using immunotherapy increase immunogenicity and enhance anticancer immune responses, including anti-GD2 antibodies; checkpoint inhibitors; drugs which macrophage natural killer T (NKT) cell function; modulation of cyclic GMP-AMP synthase-stimulator interferon genes pathway; engineering neuroblastoma-targeting chimeric-antigen receptor-T cells. Some these strategies strong preclinical foundation are being tested clinically, although none demonstrated notable success in treating paediatric neuroblastoma date. Recently, approaches overcome heterogeneity tumours resistance explored. These include rational combination aim achieving synergy, such as dual targeting GD2 tumour-associated macrophages or cells; B7-H3 checkpoint; enhancer zeste-2 methyltransferase inhibitors. Such provide opportunities primary maximize benefits neuroblastoma.

Language: Английский

Citations

14
Engineering CAR-T therapies for autoimmune disease and beyond DOI Open Access
Emily P. English, Robert Swingler,

Simran Patwa

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(771)

Published: Oct. 30, 2024

Chimeric antigen receptor–T cell (CAR-T) therapy has transformed the management of refractory hematological malignancies. Now that targeting pathogenic cells interest with antigen-directed cytotoxic T lymphocytes is possible, field expanding reach CAR-T beyond oncology. Recently, breakthrough progress been made in application technology to autoimmune diseases, exploiting same validated targets were used by pioneering therapies hematology. Here, we discuss recent advances and outcomes are paving way for extension new therapeutic areas, including autoimmunity.

Language: Английский

Citations

6
Alloreactive-free CAR-VST therapy: a step forward in long-term tumor control in viral context DOI Creative Commons
Valentine Wang, Barbara Savoldo, J. Guimarães

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

CAR-T cell therapy has revolutionized immunotherapy but its allogeneic application, using various strategies, faces significant challenges including graft-versus-host disease and graft rejection. Recent advances Virus Specific T cells to generate CAR-VST have demonstrated potential for enhanced persistence antitumor efficacy, positioning CAR-VSTs as a promising alternative conventional in an setting. This review provides comprehensive overview of development, emphasizing strategies mitigate immunogenicity, such specialized TCR, approaches improve therapeutic against host immune responses. In this review, we discuss the production methods explore optimization enhance their functionality, activation profiles, memory persistence, exhaustion resistance. Emphasis is placed on unique dual specificity both antiviral responses, along with in-depth examination preclinical clinical outcomes. We highlight how these contribute efficacy durability settings, offering new perspectives broad applications. By focusing key mechanisms that enable address autologous challenges, highlights strategy developing effective therapies.

Language: Английский

Citations

0
The potential of chimeric antigen receptor -T cell therapy for endocrine cancer DOI Creative Commons

Ruonan Yu,

Xiaoyu Ji, Ping Zhang

et al.

World Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 22, 2025

Language: Английский

Citations

0