CAR-T Therapy Beyond B-Cell Hematological Malignancies DOI Creative Commons
Martina Canichella, Paolo de Fabritiis

Cells, Journal Year: 2025, Volume and Issue: 14(1), P. 41 - 41

Published: Jan. 3, 2025

Despite the advances of CAR-T cells in certain hematological malignancies, mostly from B-cell derivations such as non-Hodgkin lymphomas, acute lymphoblastic leukemia and multiple myeloma, a significant portion other non-hematological pathologies can benefit this innovative treatment, results clinical studies are demonstrating. The application setting T-lymphoid leukemia, myeloid solid tumors, autoimmune diseases infections has encountered limitations that different those diseases. To overcome these restrictions, strategies based on molecular engineering platforms have been devised will be illustrated below. aim manuscript is to provide an overview than currently treated, highlighting both limits obtained with settings.

Language: Английский

Genetic engineering of T cells for immunotherapy DOI
Gavin I. Ellis, Neil C. Sheppard, James L. Riley

et al.

Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 22(7), P. 427 - 447

Published: Feb. 18, 2021

Language: Английский

Citations

110

Orthogonal Design of Experiments for Optimization of Lipid Nanoparticles for mRNA Engineering of CAR T Cells DOI
Margaret M. Billingsley, Alex G. Hamilton, David Mai

et al.

Nano Letters, Journal Year: 2021, Volume and Issue: 22(1), P. 533 - 542

Published: Oct. 20, 2021

Viral engineered chimeric antigen receptor (CAR) T cell therapies are potent, targeted cancer immunotherapies, but their permanent CAR expression can lead to severe adverse effects. Nonviral messenger RNA (mRNA) cells being explored overcome these drawbacks, electroporation, the most common transfection method, is limited by cytotoxicity. As a potentially safer nonviral delivery strategy, here, sequential libraries of ionizable lipid nanoparticle (LNP) formulations with varied excipient compositions were screened in comparison standard formulation for improved mRNA low cytotoxicity, revealing B10 as top 3-fold increase delivery. When compared electroporation primary human cells, LNPs induced comparable reduced cytotoxicity while demonstrating potent killing. These results demonstrate impact optimization on LNP performance and support platform engineering.

Language: Английский

Citations

109

Ionizable Lipid Nanoparticles with Integrated Immune Checkpoint Inhibition for mRNA CAR T Cell Engineering DOI Open Access
Alex G. Hamilton, Kelsey L. Swingle, Ryann A. Joseph

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(30)

Published: Aug. 21, 2023

The programmed cell death protein 1 (PD-1) signaling pathway is a major source of dampened T activity in the tumor microenvironment. While clinical approaches to inhibiting PD-1 using antibody blockade have been broadly successful, these lead widespread suppression, increasing risk autoimmune reactions. This study reports development an ionizable lipid nanoparticle (LNP) platform for simultaneous therapeutic gene expression and RNA interference (RNAi)-mediated transient knockdown cells. In developing this platform, interesting interactions are observed between two cargoes when co-encapsulated, leading improved characteristics compared delivering either cargo alone. messenger (mRNA)/small interfering (siRNA) co-delivery adopted deliver chimeric antigen receptor (CAR) mRNA siRNA targeting primary human cells ex vivo strong CAR without apparent changes overall activation state. delivery shows great promise immune modulation number immunoengineering applications, including cancer immunotherapies.

Language: Английский

Citations

46

Antigen Presenting Cell Mimetic Lipid Nanoparticles for Rapid mRNA CAR T Cell Cancer Immunotherapy DOI Creative Commons
Ann E. Metzloff, Marshall S. Padilla, Ningqiang Gong

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(26)

Published: Feb. 29, 2024

Abstract Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable clinical success in the treatment of hematological malignancies. However, producing these bespoke cancer‐killing cells is a complicated ex vivo process involving leukapheresis, artificial activation, and CAR construct introduction. The activation step requires engagement CD3/TCR CD28 vital for transfection differentiation. Though antigen‐presenting (APCs) facilitate vivo, relies on antibodies against CD3 conjugated to magnetic beads. While effective, this adds complexity production as beads must be removed prior implementation. To overcome challenge, work develops activating lipid nanoparticles (aLNPs) that mimic APCs combine capabilities LNPs. It shown aLNPs enable one‐step primary human with resulting mRNA reducing tumor burden murine xenograft model, validating promising platform rapid cells.

Language: Английский

Citations

31

Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection DOI Creative Commons
Wenli Mu,

Vaibhavi Patankar,

Scott G. Kitchen

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 219 - 219

Published: Jan. 31, 2024

Chronic Human Immunodeficiency Virus (HIV) infection remains a significant challenge to global public health. Despite advances in antiretroviral therapy (ART), which has transformed HIV from fatal disease into manageable chronic condition, definitive cure elusive. One of the key features is immune activation and inflammation, are strongly associated with, predictive of, progression, even patients successfully treated with suppressive ART. inflammation characterized by persistent cell metabolic dysregulation, cellular exhaustion dysfunction. This review aims summarize current knowledge interplay between metabolism, T dysfunction infection, also discusses use humanized mice models study pathogenesis develop novel therapeutic strategies.

Language: Английский

Citations

26

Enhancing CAR Macrophage Efferocytosis Via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling DOI Creative Commons

Skylar T. Chuang,

Joshua B. Stein,

Sarah Nevins

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(19)

Published: Feb. 14, 2024

The removal of dying cells, or efferocytosis, is an indispensable part resolving inflammation. However, the inflammatory microenvironment atherosclerotic plaque frequently affects biology both apoptotic cells and resident phagocytes, rendering efferocytosis dysfunctional. To overcome this problem, a chimeric antigen receptor (CAR) macrophage that can target engulf phagocytosis-resistant expressing CD47 developed. In normal circumstances, CAR macrophages exhibit activity equivalent to antibody blockage. surface modified with reactive oxygen species (ROS)-responsive therapeutic nanoparticles targeting liver X pathway improve their cell effector activities. combination nanoparticle engineering activated lipid efflux pumps enhances debris clearance reduces It further suggested undifferentiated CAR-Ms transmigrate within mico-fabricated vessel system. also shown our act as switch (CSR) withstand immunosuppressive environment. developed platform has potential contribute advancement next-generation cardiovascular disease therapies studies include in vivo experiments.

Language: Английский

Citations

24

Clinical development of CAR T cell therapy in China: 2020 update DOI Creative Commons
Jianshu Wei,

Yelei Guo,

Yao Wang

et al.

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 18(4), P. 792 - 804

Published: Sept. 30, 2020

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in the treatment of hematological malignancies. In recent years, fast-growing CAR T clinical trials have actively explored their potential application scenarios. According to data from clinicaltrials.gov website, China became country with most registered September 2017. As June 30, 2020, number reached 357. addition, as many 150 other been on ChiCTR. Although is flourishing China, there are still some problems that cannot be ignored. this review, we aim systematically summarize practice China. This review will provide an informative reference for colleagues field, and a better understanding history current situation help us more reasonably conduct research promote cooperation.

Language: Английский

Citations

76

Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study DOI Creative Commons

Yunyu Mao,

Qibin Liao,

Youwei Zhu

et al.

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 14, 2024

Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing CXCR5, termed M10 cells. were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, B-cell follicle homing. After demonstrating activities, administered treat 18 patients via a regimen two allogenic cell infusions an interval 30 days, each infusion followed by chidamide stimulations reservoir activation. Consequently, 74.3% resulted in significant suppression viral rebound, loads declining average 67.1%, 10 showed persistently reduced cell-associated RNA levels (average decrease 1.15 log10) over 150-day observation period. also found impose selective pressure latent reservoir. No treatment-related adverse observed. Overall, our study supported potential as novel, safe, effective option functional cure HIV-1/AIDS.

Language: Английский

Citations

16

Stem cell-derived CAR T cells show greater persistence, trafficking, and viral control compared to ex vivo transduced CAR T cells DOI Creative Commons
Mayra A. Carrillo, Anjie Zhen, Wenli Mu

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(4), P. 1000 - 1015

Published: Feb. 27, 2024

Adoptive cell therapy (ACT) using T cells expressing chimeric antigen receptors (CARs) is an area of intense investigation in the treatment malignancies and chronic viral infections. One limitations ACT-based CAR lack vivo persistence maintenance optimal function. Therefore, alternative strategies that increase function CAR-expressing are needed. In our studies humanized bone marrow/liver/thymus (BLT) mouse model nonhuman primate (NHP) HIV infection, we evaluated two CAR-based gene approaches. ACT approach, used cytokine enhancement preconditioning to generate greater anti-HIV

Language: Английский

Citations

11

Adoptive cell therapy for solid tumors beyond CAR-T: Current challenges and emerging therapeutic advances DOI
Tingrui Zhang, Zongguang Tai, Fengze Miao

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 368, P. 372 - 396

Published: March 6, 2024

Language: Английский

Citations

8