Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products

Nezhad, Muhammad Sadeqi; Abdollahpour‐Alitappeh, Meghdad; Rezaei, Behzad; Yazdanifar, Mahboubeh; Seifalian, Alexander M.

doi:10.1007/s11095-021-03067-z

Cited by 21 publications

(13 citation statements)

References 122 publications

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“…Almost all somatic cell types have been successfully re-programmed to achieve pluripotency through the introduction of specific sets of reprogramming factors. These comprise the co-expression of OCT3/4, SOX2, KLF4 and c-MYC (Takahashi et al 2007 ) or OCT4, SOX2, NANOG, and LIN28, a combination that is believed to be less tumorigenic (Sadeqi Nezhad et al 2021 ; Yu et al 2007 ). Delivery of reprogramming factors may be achieved using traditional integrating viral vectors (e.g., retrovirus or lentivirus) or non-integrating systems (e.g., episomal, minicircle or transposon-based vectors, Sendai virus, plasmids, mRNA or microRNAs) that minimise risk of insertional mutagenesis (Sadeqi Nezhad et al 2021 ).…”

Section: Induced Pluripotent Stem Cell Technologymentioning

confidence: 99%

“…These comprise the co-expression of OCT3/4, SOX2, KLF4 and c-MYC (Takahashi et al 2007 ) or OCT4, SOX2, NANOG, and LIN28, a combination that is believed to be less tumorigenic (Sadeqi Nezhad et al 2021 ; Yu et al 2007 ). Delivery of reprogramming factors may be achieved using traditional integrating viral vectors (e.g., retrovirus or lentivirus) or non-integrating systems (e.g., episomal, minicircle or transposon-based vectors, Sendai virus, plasmids, mRNA or microRNAs) that minimise risk of insertional mutagenesis (Sadeqi Nezhad et al 2021 ). Successful generation of iPSCs can be confirmed by the detection of a panel of cell surface and intracellular markers associated with pluripotency (Sadeqi Nezhad et al 2021 ).…”

Section: Induced Pluripotent Stem Cell Technologymentioning

confidence: 99%

“…This opportunity also eliminates batch to batch variability that may arise due to genetic editing. Fourth, iPSC cell banks are amenable to extensive characterisation to ensure safety and suitability for clinical use (Sadeqi Nezhad et al 2021 ) (Fig. 2 ).…”

Section: Induced Pluripotent Stem Cell Technologymentioning

confidence: 99%

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Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies

Mazza

Maher

2021

Arch. Immunol. Ther. Exp.

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Technologies required to generate induced pluripotent stem cells (iPSC) were first described 15 years ago, providing a strong impetus to the field of regenerative medicine. In parallel, immunotherapy has finally emerged as a clinically meaningful modality of cancer therapy. In particular, impressive efficacy has been achieved in patients with selected haematological malignancies using ex vivo expanded autologous T cells engineered to express chimeric antigen receptors (CARs). While solid tumours account for over 90% of human cancer, they currently are largely refractory to this therapeutic approach. Nonetheless, given the considerable innovation taking place worldwide in the CAR field, it is likely that effective solutions for common solid tumours will emerge in the near future. Such a development will create significant new challenges in the scalable delivery of these complex, costly and individualised therapies. CAR-engineered immune cell products that originate from iPSCs offer the potential to generate unlimited numbers of homogeneous, standardised cell products in which multiple defined gene modification events have been introduced to ensure safety, potency and reproducibility. Here, we review some of the emerging strategies in use to engineer CAR-expressing iPSC-derived drug products.

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Section: Induced Pluripotent Stem Cell Technologymentioning

confidence: 99%

Section: Induced Pluripotent Stem Cell Technologymentioning

confidence: 99%

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Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies

Mazza

Maher

2021

Arch. Immunol. Ther. Exp.

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“…Furthermore, the use of umbilical cord blood-derived CAR T cells could be associated with reduced risk and severity of GvHD due to their antigen-naive status and impaired NFAT signaling [ 188 ]. In principle, CAR T cells may also be obtained from induced pluripotent stem cells (iPSCs) with a theoretically unlimited capacity to self-renew [ 189 ]. Furthermore, in patients who received allogeneic stem cell transplantation but experience a relapse, CAR T cells can be engineered from the original stem cell donor to strengthen the graft-versus-tumor effect while limiting the risk of GvHD [ 190 ].…”

Section: Adoptive T Cell Transfer Therapy—a Focus On Car T Cellsmentioning

confidence: 99%

T Cell Engaging Immunotherapies, Highlighting Chimeric Antigen Receptor (CAR) T Cell Therapy

Bousser

Callewaert

Festjens

2021

Cancers

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In the past decade, chimeric antigen receptor (CAR) T cell technology has revolutionized cancer immunotherapy. This strategy uses synthetic CARs to redirect the patient’s own immune cells to recognize specific antigens expressed on the surface of tumor cells. The unprecedented success of anti-CD19 CAR T cell therapy against B cell malignancies has resulted in its approval by the US Food and Drug Administration (FDA) in 2017. However, major scientific challenges still remain to be addressed for the broad use of CAR T cell therapy. These include severe toxicities, limited efficacy against solid tumors, and immune suppression in the hostile tumor microenvironment. Furthermore, CAR T cell therapy is a personalized medicine of which the production is time- and resource-intensive, which makes it very expensive. All these factors drive new innovations to engineer more powerful CAR T cells with improved antitumor activity, which are reviewed in this manuscript.

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“…In a few cancer sorts (e.g., ALL), the treatment may fall flat in patients analyzed with fast dynamic illness who require an quick treatment with CAR-T cells due to the long-time autologous CAR-T fabricating handle. Furthermore, the satisfactory number of T cell collections from patients with hematologic threat is now and then difficult and impracticable due to lymphopenia from later or earlier chemotherapy or fundamental infection [12] [13].In the interim, there are other issues related with CAR-T cell treatment, counting antigen elude, destitute trafficking and tumor invasion, low determination, restraint and resistance of T cells, and CAR-T relate clinical toxicities [14].Importantly, obstacles such as cost of treatment, gap between leukapheresis and manufacturing,and specific inclusion and exclusion criteria set by clinical trial restrict patients from getting the treatment [15].Moreover, CAR-T treatment has too been utilized against strong tumors and appeared promising helpful approaches; in any case, up to presently FDA endorsed no CAR-T items for strong tumors. This means that the challenges in strong tumors are much more genuine and require an exhaustive examination.…”

Section: Introductionmentioning

confidence: 99%

CRISPR and CAR-T, NK Current application and future perspective

khoshandam¹,

Khoshandam

Soltaninejad

et al. 2022

Preprint

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Chimeric Antigen Receptor T-cells represent a breakthrough in personalized cancer therapy. In this strategy, synthetic receptors comprised of antigen recognition, signaling, and stimulatory domains are used to reprogram T-cells to target tumor cells for destruction. Despite the success of this approach in refractory B-cell malignancies, optimal potency of CAR T-cell therapy for many other cancers, particularly solid tumors, has not been achieved. NK cells are powerful cytotoxic lymphocytes specialized in recognizing and dispensing with changed cells, and in coordinating versatile anti-tumor immunity.NK cells are as a rule practically depleted within the tumor microenvironment. In like manner, current investigate endeavors center on exactness designing of CAR T-cells with routine CRISPR-Cas9 frameworks or novel editors that can introduce craved hereditary changes with or without presentation of a double-stranded break into the genome. These instruments and methodologies can be specifically connected to focusing on negative controllers of T-cell work, coordinating helpful transgenes to particular genomic loci, and producing reproducibly secure and powerful allogeneic widespread CAR T-cell items for on-demand cancer immunotherapy. The revelation and improvement of the CRISPR/Cas9 innovation offer an adaptable and proficient gene-editing capability in tweaking different pathways that intercede NK cell fatigue and in outfitting NK cells with novel chimeric antigen receptors to particularly target tumor cells. Despite the tall productivity in its geneediting capability, trouble within the conveyance of the CRISPR/Cas9 framework remains a major bottleneck for its restorative applications, especially for NK cells.This review assesses a few of the progressing and future bearings of combining next-generation CRISPR-Cas9 quality altering with manufactured science to optimize CAR T-cell and NK cell treatment for future clinical trials toward the foundation of a modern cancer treatment parade.

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Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products

Cited by 21 publications

References 122 publications

Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies

Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies

T Cell Engaging Immunotherapies, Highlighting Chimeric Antigen Receptor (CAR) T Cell Therapy

CRISPR and CAR-T, NK Current application and future perspective

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