The paths toward non-viral CAR-T cell manufacturing: A comprehensive review of state-of-the-art methods

Metanat, Yekta; Viktor, Patrik; Amajd, Ayesha; Kaur, Irwanjot; Hamed, Ashraf Mohammed; Abed Al-Abadi, Noor K.; Alwan, Nathera Hussin; Chaitanya, M.V.N.L.; Lakshmaiya, Natrayan; Ghildiyal, Pallavi; Khalaf, Othman Mahjoob; Ciongradi, Carmen Iulia; Sârbu, Ioan

doi:10.1016/j.lfs.2024.122683

Cited by 4 publications

(1 citation statement)

References 246 publications

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“…Considering the impossibility of evaluating all edited cells and the technical limit of molecular methods, it is necessary to combine molecular assays with functional assessments ( 175 ). Currently, in vivo tumorigenicity assays are widely used to evaluate tumorigenicity of genome edited cells.…”

Section: Considerations and Risk Assessment In Genome-edited Car-t Ce...mentioning

confidence: 99%

Progress and pitfalls of gene editing technology in CAR-T cell therapy: a state-of-the-art review

Moradi,

Khodabandehloo,

Alidadi

et al. 2024

Front. Oncol.

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CAR-T cell therapy has shown remarkable promise in treating B-cell malignancies, which has sparked optimism about its potential to treat other types of cancer as well. Nevertheless, the Expectations of CAR-T cell therapy in solid tumors and non-B cell hematologic malignancies have not been met. Furthermore, safety concerns regarding the use of viral vectors and the current personalized production process are other bottlenecks that limit its widespread use. In recent years the use of gene editing technology in CAR-T cell therapy has opened a new way to unleash the latent potentials of CAR-T cell therapy and lessen its associated challenges. Moreover, gene editing tools have paved the way to manufacturing CAR-T cells in a fully non-viral approach as well as providing a universal, off-the-shelf product. Despite all the advantages of gene editing strategies, the off-target activity of classical gene editing tools (ZFNs, TALENs, and CRISPR/Cas9) remains a major concern. Accordingly, several efforts have been made in recent years to reduce their off-target activity and genotoxicity, leading to the introduction of advanced gene editing tools with an improved safety profile. In this review, we begin by examining advanced gene editing tools, providing an overview of how these technologies are currently being applied in clinical trials of CAR-T cell therapies. Following this, we explore various gene editing strategies aimed at enhancing the safety and efficacy of CAR-T cell therapy.

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Section: Considerations and Risk Assessment In Genome-edited Car-t Ce...mentioning

confidence: 99%

Progress and pitfalls of gene editing technology in CAR-T cell therapy: a state-of-the-art review

Moradi,

Khodabandehloo,

Alidadi

et al. 2024

Front. Oncol.

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Potential alternatives to αβ-T cells to prevent graft-versus-host disease (GvHD) in allogeneic chimeric antigen receptor (CAR)-based cancer immunotherapy: A comprehensive review

Tang,

Zhang

2024

Pathology - Research and Practice

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Focusing on exosomes to overcome the existing bottlenecks of CAR-T cell therapy

Zhang,

Peng,

Chen

et al. 2024

Inflamm Regener

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Since chimeric antigen receptor T (CAR-T) cells were introduced three decades ago, the treatment using these cells has led to outstanding outcomes, and at the moment, CAR-T cell therapy is a well-established mainstay for treating CD19 + malignancies and multiple myeloma. Despite the astonishing results of CAR-T cell therapy in B-cell-derived malignancies, several bottlenecks must be overcome to promote its safety and efficacy and broaden its applicability. These bottlenecks include cumbersome production process, safety concerns of viral vectors, poor efficacy in treating solid tumors, life-threatening side effects, and dysfunctionality of infused CAR-T cells over time. Exosomes are nano-sized vesicles that are secreted by all living cells and play an essential role in cellular crosstalk by bridging between cells. In this review, we discuss how the existing bottlenecks of CAR-T cell therapy can be overcome by focusing on exosomes. First, we delve into the effect of tumor-derived exosomes on the CAR-T cell function and discuss how inhibiting their secretion can enhance the efficacy of CAR-T cell therapy. Afterward, the application of exosomes to the manufacturing of CAR-T cells in a non-viral approach is discussed. We also review the latest advancements in ex vivo activation and cultivation of CAR-T cells using exosomes, as well as the potential of engineered exosomes to in vivo induction or boost the in vivo proliferation of CAR-T cells. Finally, we discuss how CAR-engineered exosomes can be used as a versatile tool for the direct killing of tumor cells or delivering intended therapeutic payloads in a targeted manner.

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The paths toward non-viral CAR-T cell manufacturing: A comprehensive review of state-of-the-art methods

Cited by 4 publications

References 246 publications

Progress and pitfalls of gene editing technology in CAR-T cell therapy: a state-of-the-art review

Progress and pitfalls of gene editing technology in CAR-T cell therapy: a state-of-the-art review

Potential alternatives to αβ-T cells to prevent graft-versus-host disease (GvHD) in allogeneic chimeric antigen receptor (CAR)-based cancer immunotherapy: A comprehensive review

Focusing on exosomes to overcome the existing bottlenecks of CAR-T cell therapy

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