Engineering of regulatory T cells by means of mRNA electroporation in a GMP-compliant manner

Janssens, Ibo; Davó, Diana Campillo; Bos, Jasper Van den; Reu, Hans De; Berneman, Zwi; Wens, Inez; Cools, Nathalie

doi:10.1016/j.jcyt.2022.01.001

Cited by 8 publications

(7 citation statements)

References 84 publications

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“…In addition, the inflammatory microenvironment which is often observed in MS and SCI is unfavourable for CNS repair and can be adapted by the administration of anti-inflammatory cells such as regulatory T cells, which are currently extensively tested in the clinic [ 128 , 129 , 130 ]. These cells can be easily engineered to overexpress neuroprotective factors such as neurotrophins, thereby improving their neuroregenerative and neuroprotective properties [ 131 , 132 ]. Optimizing and combining different therapeutic strategies will possibly bring a solution for neurodegenerative diseases in the future.…”

Section: Discussionmentioning

confidence: 99%

Are Cell-Based Therapies Safe and Effective in the Treatment of Neurodegenerative Diseases? A Systematic Review with Meta-Analysis

et al. 2022

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Over the past two decades, significant advances have been made in the field of regenerative medicine. However, despite being of the utmost clinical urgency, there remains a paucity of therapeutic strategies for conditions with substantial neurodegeneration such as (progressive) multiple sclerosis (MS), spinal cord injury (SCI), Parkinson’s disease (PD) and Alzheimer’s disease (AD). Different cell types, such as mesenchymal stromal cells (MSC), neuronal stem cells (NSC), olfactory ensheathing cells (OEC), neurons and a variety of others, already demonstrated safety and regenerative or neuroprotective properties in the central nervous system during the preclinical phase. As a result of these promising findings, in recent years, these necessary types of cell therapies have been intensively tested in clinical trials to establish whether these results could be confirmed in patients. However, extensive research is still needed regarding elucidating the exact mechanism of action, possible immune rejection, functionality and survival of the administered cells, dose, frequency and administration route. To summarize the current state of knowledge, we conducted a systematic review with meta-analysis. A total of 27,043 records were reviewed by two independent assessors and 71 records were included in the final quantitative analysis. These results show that the overall frequency of serious adverse events was low: 0.03 (95% CI: 0.01–0.08). In addition, several trials in MS and SCI reported efficacy data, demonstrating some promising results on clinical outcomes. All randomized controlled studies were at a low risk of bias due to appropriate blinding of the treatment, including assessors and patients. In conclusion, cell-based therapies in neurodegenerative disease are safe and feasible while showing promising clinical improvements. Nevertheless, given their high heterogeneity, the results require a cautious approach. We advocate for the harmonization of study protocols of trials investigating cell-based therapies in neurodegenerative diseases, adverse event reporting and investigation of clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Are Cell-Based Therapies Safe and Effective in the Treatment of Neurodegenerative Diseases? A Systematic Review with Meta-Analysis

et al. 2022

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“… Scaffold-based biomaterials Application(s) Biomaterial(s) used Strategy (es) Result(s) Ref. Beta-islet transplantation T1D GelMA hydrogel Functionalization of hydrogel with IL-2 and CCL-1 Encapsulation of natural and induced Tregs into functionalized hydrogel Retention of Treg viability, stable phenotype, and function within hydrogel Inclusion of Tregs and attraction of CCR-8+ Tregs within hydrogel [ 77 ] Nerve allografts PEGNB biodegradable hydrogel Encapsulation of Tregs into hydrogel Transplantation of hydrogel containing Tregs around nerves' allografts Gradual release of Tregs from the hydrogel into the graft Suppression of host immune response Promotion of nerve regeneration in recipients [ 142 ] Isolation of Tregs Facilitate ex vivo isolation, activation, and expansion of Foxp3+/CD4+/CD25+ Tregs Study the behaviors of Tregs Superparamagnetic particles (Dynabeads™ Treg CD3/CD28) Optimization of Dynabeads™ Treg for isolation, activation and expansion of Foxp3+/CD4+/CD25+ Tregs Several hundred-fold expansions of Treg cell populations Isolation of Tregs with high expression of Foxp3 and suppressive activity [ 143 ] Soluble polymer nanomatrix Polymer conjugation with anti-CD3 and anti-CD28 Inclusion of a high amount of exogenous IL-2 Isolation of CD4+/CD127-/CD25+/CD45RA+ and CD4+/CD127-/CD25hi Treg subsets Enhancement of Treg functions during in vitro expansion [ …”

Section: Biomaterials To Facilitate Enhancement In Treg Functionsmentioning

confidence: 99%

Biomaterial-enhanced treg cell immunotherapy: A promising approach for transplant medicine and autoimmune disease treatment

Mashayekhi,

Khazaie,

Faubion

et al. 2024

Bioactive Materials

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“…This means that iTreg cells will lose their suppressive function by reducing Foxp3 expression in the absence of stimulating cytokines [140]. However, several pieces of evidence show that it is possible to expand Treg cells which have effective suppressive functions in vitro based on good manufacturing practice-compliant (GMP-compliant) protocols [141][142][143][144][145][146][147][148]. These GMP-compliant protocols can be used for adoptive Treg cell transfer.…”

Section: Limitations Challenges and Opportunities For Treg-based Ther...mentioning

confidence: 99%

Regulatory T cells in rheumatoid arthritis: functions, development, regulation, and therapeutic potential

Yan

Kotschenreuther

Deng

et al. 2022

Cell. Mol. Life Sci.

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Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects the joints but also leads to systemic inflammation. Auto-reactivity and dysregulation of self-tolerance are thought to play a vital role in disease onset. In the pathogenesis of autoimmune diseases, disturbed immunosuppressive properties of regulatory T cells contribute to the dysregulation of immune homeostasis. In RA patients, the functions of Treg cells and their frequency are reduced. Therefore, focusing on the re-establishment of self-tolerance by increasing Treg cell frequencies and preventing a loss of function is a promising strategy for the treatment of RA. This approach could be especially beneficial for those patients who do not respond well to current therapies. In this review, we summarize and discuss the current knowledge about the function, differentiation and regulation of Treg cells in RA patients and in animal models of autoimmune arthritis. In addition, we highlight the therapeutic potential as well as the challenges of Treg cell targeting treatment strategies.

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Engineering of regulatory T cells by means of mRNA electroporation in a GMP-compliant manner

Cited by 8 publications

References 84 publications

Are Cell-Based Therapies Safe and Effective in the Treatment of Neurodegenerative Diseases? A Systematic Review with Meta-Analysis

Are Cell-Based Therapies Safe and Effective in the Treatment of Neurodegenerative Diseases? A Systematic Review with Meta-Analysis

Biomaterial-enhanced treg cell immunotherapy: A promising approach for transplant medicine and autoimmune disease treatment

Regulatory T cells in rheumatoid arthritis: functions, development, regulation, and therapeutic potential

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