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. 2021 Apr 1;105(4):832-841.
doi: 10.1097/TP.0000000000003315.

Preclinical Assessment of Autologous Tolerogenic Dendritic Cells From End-stage Renal Disease Patients

Laurence Bouchet-Delbos  1 , Amandine Even  1 , Emilie Varey  1 , Soraya Saïagh  2 , Sylvain Bercegeay  2 , Cécile Braudeau  1   3 , Brigitte Dréno  2 , Gilles Blancho  1 , Régis Josien  1   3 , Maria-Cristina Cuturi  1   4 , Aurélie Moreau  1   4
Affiliations

Preclinical Assessment of Autologous Tolerogenic Dendritic Cells From End-stage Renal Disease Patients

Laurence Bouchet-Delbos et al. Transplantation. .

Abstract

Background: Kidney transplantation is the therapeutic of choice for patients with kidney failure. While immunosuppressive drugs can control graft rejection, their use is associated with increased infections and cancer, and they do not effectively control chronic graft rejection. Cell therapy is an attractive strategy to minimize the use of pharmacological drugs.

Methods: We recently developed a protocol to generate human monocyte-derived autologous tolerogenic dendritic cells (ATDCs) from healthy volunteers. Herein, we transferred the ATDC manufacturing protocol to a Good Manufacturing Practice (GMP)-compliant facility. Furthermore, we compared the phenotype and in vitro functions of ATDCs generated from patients with end-stage renal disease to those generated from healthy volunteers.

Results: We describe the critical steps for GMP-compliant production of ATDCs and define the quality criteria required to allow release of the cell products. Furthermore, we showed that ATDCs generated from healthy volunteers and patients with kidney failure display the same tolerogenic profile based on their phenotype, resistance to maturation, and ability to modulate T-cell responses.

Conclusions: Together, these results allowed us to define the production process and the quality criteria for the release of ATDCs before their administration in patients receiving a kidney transplant.

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Conflict of interest statement

The authors declare no conflicts of interest.

References

    1. Marín E, Cuturi MC, Moreau A. Tolerogenic dendritic cells in solid organ transplantation: where do we stand? Front Immunol. 2018; 9:274
    1. Lutz MB, Suri RM, Niimi M, et al. Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo. Eur J Immunol. 2000; 30:1813–1822
    1. Turnquist HR, Raimondi G, Zahorchak AF, et al. Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote organ transplant tolerance. J Immunol. 2007; 178:7018–7031
    1. Lan YY, Wang Z, Raimondi G, et al. “Alternatively activated” dendritic cells preferentially secrete IL-10, expand Foxp3+CD4+ T cells, and induce long-term organ allograft survival in combination with CTLA4-Ig. J Immunol. 2006; 177:5868–5877
    1. Baas MC, Kuhn C, Valette F, et al. Combining autologous dendritic cell therapy with CD3 antibodies promotes regulatory T cells and permanent islet allograft acceptance. J Immunol. 2014; 193:4696–4703

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