Minimum information about tolerogenic antigen-presenting cells (MITAP): a first step towards reproducibility and standardisation of cellular therapies

Lord, Phillip; Spiering, Rachel; Aguillón, Juan Carlos; Anderson, Amy E.; Appel, Silke; Benítez‐Ribas, Daniel; Brinke, Anja ten; Broere, Femke; Cools, Nathalie; Cuturi, María Cristina; Diboll, Julie; Geissler, Edward K.; Giannoukakis, Nick; Gregori, Silvia; Ham, S. Marieke van; Lattimer, Staci; Marshall, Lindsay J.; Harry, Rachel A.; Hutchinson, James A.; Isaacs, John D.; Joosten, Irma; Kooten, Cees van; Cerio, Ascension Lopez Diaz de; Nikolić, Tatjana; Oral, Haluk Barbaros; Sofronić-Milosavljević, Ljiljana; Ritter, Thomas; Riquelme, Paloma; Thomson, Angus W.; Trucco, Massimo; Vives-Pi, Marta; Martı́nez-Cáceres, Eva; Hilkens, Catharien M. U.

doi:10.7717/peerj.2300

Cited by 43 publications

(43 citation statements)

References 19 publications

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“…The difficulty in comparing the characteristics of different clinical tDC does suggest the need for an uniform set of metrics for their description. This was the focus of the minimum information about tolerogenic antigen-presenting cells ( 103 ) initiative whose authors included members from a number of the completed and ongoing clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease

et al. 2017

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Tolerogenic dendritic cell (tDC)-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat autoimmune diseases of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis (MS), and Crohn’s disease. This review will address tDC employed in current clinical trials, focusing on cell characteristics, mechanisms of action, and clinical findings. To date, the publicly reported human trials using tDC indicate that regulatory lymphocytes (largely Foxp3+ T-regulatory cell and, in one trial, B-regulatory cells) are, for the most part, increased in frequency in the circulation. Other than this observation, there are significant differences in the major phenotypes of the tDC. These differences may affect the outcome in efficacy of recently launched and impending phase II trials. Recent efforts to establish a catalog listing where tDC converge and diverge in phenotype and functional outcome are an important first step toward understanding core mechanisms of action and critical “musts” for tDC to be therapeutically successful. In our view, the most critical parameter to efficacy is in vivo stability of the tolerogenic activity over phenotype. As such, methods that generate tDC that can induce and stably maintain immune hyporesponsiveness to allo- or disease-specific autoantigens in the presence of powerful pro-inflammatory signals are those that will fare better in primary endpoints in phase II clinical trials (e.g., disease improvement, preservation of autoimmunity-targeted tissue, allograft survival). We propose that pre-treatment phenotypes of tDC in the absence of functional stability are of secondary value especially as such phenotypes can dramatically change following administration, especially under dynamic changes in the inflammatory state of the patient. Furthermore, understanding the outcomes of different methods of cell delivery and sites of delivery on functional outcomes, as well as quality control variability in the functional outcomes resulting from the various approaches of generating tDC for clinical use, will inform more standardized ex vivo generation methods. An understanding of these similarities and differences, with a reference point the large number of naturally occurring tDC populations with different immune profiles described in the literature, could explain some of the expected and unanticipated outcomes of emerging tDC clinical trials.

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Section: Discussionmentioning

confidence: 99%

Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease

et al. 2017

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“…The minimum information about tolerogenic antigen-presenting cells (MITAP) checklist (32) was followed for the preparation of this manuscript.…”

Section: Methodsmentioning

confidence: 99%

Treatment with Dexamethasone and Monophosphoryl Lipid A Removes Disease-Associated Transcriptional Signatures in Monocyte-Derived Dendritic Cells from Rheumatoid Arthritis Patients and Confers Tolerogenic Features

et al. 2016

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Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA), referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties, and T cell-stimulatory capacity in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of co-stimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating toward the lymphoid chemokines CXCL12 and CCL19. These MPLA-tDCs induced hyporesponsiveness of autologous CD4+ T cells specific for synovial antigens in vitro. Global transcriptome analysis confirmed a unique transcriptional profile of MPLA-tDCs and revealed that RA-associated genes, which were upregulated in untreated DCs from RA patients, returned to expression levels of healthy donor-derived DCs after treatment with dexamethasone and MPLA. Thus, monocyte-derived DCs from RA patients have the capacity to develop tolerogenic features at transcriptional as well as at translational level, when modulated with dexamethasone and MPLA, overcoming disease-related effects. Furthermore, the ability of MPLA-tDCs to impair T cell responses to synovial antigens validates their potential as cellular treatment for RA.

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“…As there are diverse methods of generating tolDCs and other types of tolerogenic APC (tolAPCs), a minimum information model for tolAPC (MITAP) was generated. MITAP enables researchers to report their data in a standardized and more transparent manner, facilitating data comparison and interpretation, ultimately paving the way for the development of standardized protocols for the production of tolDCs and other tolAPCs for therapeutic application . A number of tolDCs have been tested in phase I clinical trials, including for type I diabetes, Crohn's disease and RA .…”

Section: Tolerogenic Dendritic Cells As a Therapeutic Toolmentioning

confidence: 99%

“…MITAP enables researchers to report their data in a standardized and more transparent manner, facilitating data comparison and interpretation, ultimately paving the way for the development of standardized protocols for the production of tolDCs and other tolAPCs for therapeutic application. 38 A number of tolDCs have been tested in phase I clinical trials, including for type I diabetes, 30 Crohn's disease 39 and RA. 40,41 Encouragingly, tolDC therapy in all these studies was found to be feasible and safe, providing rationale to conduct further studies into their efficacy.…”

Section: Tolerogenic Dendritic Cells As a Therapeutic Toolmentioning

confidence: 99%

Targeting of tolerogenic dendritic cells towards heat‐shock proteins: a novel therapeutic strategy for autoimmune diseases?

et al. 2017

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SummaryTolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T-cell response while leaving other, protective, T-cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen. A possible solution is to use surrogate autoantigens for loading of tolDCs. We propose that heat-shock proteins may be a relevant surrogate antigen, as they are evolutionarily conserved between species, ubiquitously expressed in inflamed tissues and have been shown to induce regulatory T cells, ameliorating disease in various arthritis mouse models. In this review, we provide an overview on how immune tolerance may be restored by tolDCs, the problem of selecting relevant autoantigens for loading of tolDCs, and why heat-shock proteins could be used as surrogate autoantigens.

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Minimum information about tolerogenic antigen-presenting cells (MITAP): a first step towards reproducibility and standardisation of cellular therapies

Cited by 43 publications

References 19 publications

Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease

Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease

Treatment with Dexamethasone and Monophosphoryl Lipid A Removes Disease-Associated Transcriptional Signatures in Monocyte-Derived Dendritic Cells from Rheumatoid Arthritis Patients and Confers Tolerogenic Features

Targeting of tolerogenic dendritic cells towards heat‐shock proteins: a novel therapeutic strategy for autoimmune diseases?

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