Engineering chimeric autoantibody receptor T cells for targeted B cell depletion in multiple sclerosis model: An in-vitro study

Sahlolbei, Maryam; Azangou-Khyavy, Mohammadreza; Khanali, Javad; Khorsand, Babak; Shiralipour, Aref; Ahmadbeigi, Naser; Madjd, Zahra; Ghanbarian, Hossein; Ardjmand, Alireza; Hashemi, Seyed Mahmoud; Kiani, Jafar

doi:10.1016/j.heliyon.2023.e19763

Cited by 14 publications

(6 citation statements)

References 40 publications

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“…As CAR-T cell therapy continues to advance in the treatment of hematologic conditions, solid tumours, and autoimmune diseases, there is a growing interest in antigen-specific B cell depletion therapies. To date, four preclinical studies have used CAART cell therapy for autoimmune disorders: specifically for the treatment of pemphigus vulgaris [26], MuSK autoantibody-positive myasthenia gravis [27], NMDAR encephalitis [28], and experimental autoimmune encephalomyelitis (EAE) [29]. Traditional CARs incorporate a cleaved fragment of a monoclonal antibody known as a single-chain variable fragment (scFv) in the extracellular domain, whereas chimeric autoantibody receptors (CAARs) replace it with a specific antigen designed for autoantibodies [19].…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical and clinical studies have shown the efficacy of this approach in pemphigus vulgaris [26], MuSK autoantibody-positive myasthenia gravis [27], and NMDA receptor antibody encephalitis [28]. Recently, an in vitro study showed that myelin basic protein (MBP)-CAART has higher cytotoxic activity against autoreactive B cells in experimental autoimmune encephalomyelitis (EAE) [29].…”

Section: Introductionmentioning

confidence: 99%

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Precise Targeting of Autoantigen-Specific B Cells in Lupus Nephritis with Chimeric Autoantibody Receptor T Cells

Solé,

Royo,

Sandoval

et al. 2024

IJMS

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Despite conventional therapy, lupus nephritis (LN) remains a significant contributor to short- and long-term morbidity and mortality. B cell abnormalities and the production of autoantibodies against nuclear complexes like anti-dsDNA are recognised as key players in the pathogenesis of LN. To address the challenges of chronic immunosuppression associated with current therapies, we have engineered T cells to express chimeric autoantibody receptors (DNA-CAART) for the precise targeting of B cells expressing anti-dsDNA autoantibodies. T cells from LN patients were transduced using six different CAAR vectors based on their antigen specificity, including alpha-actinin, histone-1, heparan sulphate, or C1q. The cytotoxicity, cytokine production, and cell–cell contact of DNA-CAART were thoroughly investigated in co-culture experiments with B cells isolated from patients, both with and without anti-dsDNA positivity. The therapeutic effects were further evaluated using an in vitro immune kidney LN organoid. Among the six proposed DNA-CAART, DNA4 and DNA6 demonstrated superior selectively cytotoxic activity against anti-dsDNA+ B cells. Notably, DNA4-CAART exhibited improvements in organoid morphology, apoptosis, and the inflammatory process in the presence of IFNα-stimulated anti-dsDNA+ B cells. Based on these findings, DNA4-CAART emerge as promising candidates for modulating autoimmunity and represent a novel approach for the treatment of LN.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Precise Targeting of Autoantigen-Specific B Cells in Lupus Nephritis with Chimeric Autoantibody Receptor T Cells

Solé,

Royo,

Sandoval

et al. 2024

IJMS

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“…This form of network visualization led to the comprehension of connections between metabolites and studies. Next, bipartite network projection that is extensively used for compacting data about bipartite networks was obtained 23–25 . Network projection was employed to streamline bipartite networks by converting them into unipartite networks.…”

Section: Methodsmentioning

confidence: 99%

“…Next, bipartite network projection that is extensively used for compacting data about bipartite networks was obtained. 23 , 24 , 25 Network projection was employed to streamline bipartite networks by converting them into unipartite networks. This conversion aided in the more efficient analysis of the relationships within the data.…”

Section: Methodsmentioning

confidence: 99%

Metabolite signature of human malignant thyroid tissue: A systematic review and meta‐analysis

Razavi,

Khorsand,

Salehipour

et al. 2024

Cancer Medicine

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BackgroundThyroid cancer (TC) is the predominant malignancy within the endocrine system. However, the standard method for TC diagnosis lacks the capability to identify the pathological condition of all thyroid lesions. The metabolomics approach has the potential to manage this problem by identifying differential metabolites.AimsThis study conducted a systematic review and meta‐analysis of the NMR‐based metabolomics studies in order to identify significant altered metabolites associated with TC.MethodsA systematic search of published literature in any language in three databases including Embase, PubMed, and Scopus was conducted. Out of 353 primary articles, 12 studies met the criteria for inclusion in the systematic review. Among these, five reports belonging to three articles were eligible for meta‐analysis. The correlation coefficient of the orthogonal partial least squares discriminant analysis, a popular model in the multivariate statistical analysis of metabolomic data, was chosen for meta‐analysis. The altered metabolites were chosen based on the fact that they had been found in at least three studies.ResultsIn total, 49 compounds were identified, 40 of which were metabolites. The increased metabolites in thyroid lesions compared normal samples included lactate, taurine, alanine, glutamic acid, glutamine, leucine, lysine, phenylalanine, serine, tyrosine, valine, choline, glycine, and isoleucine. Lipids were the decreased compounds in thyroid lesions. Lactate and alanine were increased in malignant versus benign thyroid lesions, while, myo‐inositol, scyllo‐inositol, citrate, choline, and phosphocholine were found to be decreased. The meta‐analysis yielded significant results for three metabolites of lactate, alanine, and citrate in malignant versus benign specimens.DiscussionIn this study, we provided a concise summary of 12 included metabolomic studies, making it easier for future researchers to compare their results with the prior findings.ConclusionIt appears that the field of TC metabolomics will experience notable advancement, leading to the discovery of trustworthy diagnostic and prognostic biomarkers.

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“…82 Drugs that target B cells reactive against disease‐specific epitopes on autoantigen‐antibody immune complexes are under development. 83 Identifying ways to eliminate or suppress only the subsets of B cells and T cells reactive to lupus‐associated autoantigens remains a major goal.…”

Section: Slementioning

confidence: 99%

Potential clinical implications of molecular mimicry‐induced autoimmunity

Suliman

2024

Immunity Inflam & Disease

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BackgroundMolecular mimicry is hypothesized to be a mechanism by which autoimmune diseases are triggered. It refers to sequence or structural homology between foreign antigens and self‐antigens, which can activate cross‐reactive lymphocytes that attack host tissues. Elucidating the role of molecular mimicry in human autoimmunity could have important clinical implications.ObjectiveTo review evidence for the role of molecular mimicry in major autoimmune diseases and discuss potential clinical implications.MethodsComprehensive literature review of clinical trials, observational studies, animal models, and immunology studies on molecular mimicry in multiple sclerosis, type 1 diabetes, rheumatoid arthritis, lupus, Guillain‐Barre syndrome, autoimmune myocarditis, and primary biliary cirrhosis published from 2000–2023.ResultsSubstantial indirect evidence supports molecular mimicry as a contributor to loss of self‐tolerance in several autoimmune conditions. Proposed microbial triggers include Epstein‐Barr virus, coxsackievirus, Campylobacter jejuni, and bacterial commensals. Key mechanisms involve cross‐reactive T cells and autoantibodies induced by epitope homology between microbial and self‐antigens. Perpetuation of autoimmunity involves epitope spreading, inflammatory mediators, and genetic factors.ConclusionsMolecular mimicry plausibly explains initial stages of autoimmune pathogenesis induced by infection or microbiota disturbances. Understanding mimicry antigens and pathways could enable improved prediction, monitoring, and antigen‐specific immunotherapy for autoimmune disorders. However, definitive proof of causation in humans remains limited. Further research should focus on establishing clinical evidence and utility.

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Engineering chimeric autoantibody receptor T cells for targeted B cell depletion in multiple sclerosis model: An in-vitro study

Cited by 14 publications

References 40 publications

Precise Targeting of Autoantigen-Specific B Cells in Lupus Nephritis with Chimeric Autoantibody Receptor T Cells

Precise Targeting of Autoantigen-Specific B Cells in Lupus Nephritis with Chimeric Autoantibody Receptor T Cells

Metabolite signature of human malignant thyroid tissue: A systematic review and meta‐analysis

Potential clinical implications of molecular mimicry‐induced autoimmunity

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