Contributions
Abstract: P1193
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
While emerging evidence indicates that dendritic cells play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect of using dendritic cells as disease-modifying therapy. Indeed, since the introduction in the clinic in 1996, the clinical benefit of dendritic cell-based therapy has been well documented in numerous clinical trials in patients with cancer and infectious diseases. More recently, tolerance-inducing or tolerogenic dendritic cells (tolDC) also became a promising immunotherapeutic tool for restoring immune tolerance in several autoimmune diseases including MS. To guarantee utmost patient safety, clinical trials using cell-based medicinal products such as tolDC need to be conducted under stringent good manufacturing practice (GMP) guidelines and regulations defined by the European Union and the US Food and Drug Administration. In line with these rules and regulations, we report here a standardized method for the generation of tolDC according to GMP guidelines. Critical parameters including identity, viability, cell yield and potency were assessed. In doing so, specification limits for the final drug substance were determined using statistical process controls. For this, the results from the qualification batches following the ex vivo tolDC generation protocol were determined. In brief, our results reveal that tolDC display a maturation-resistant phenotype, indicated by a reduction of 35% or more in the upregulation of the expression of costimulatory markers as compared to control DC following cytokine-induced acivation. For functional release, tolDC should induce a reduction of at least 65% in IFN-gamma production by co-cultured T cells as compared to control DC.
In conclusion, a reproducible method for the generation of human tolDC according to GMP guidelines is described with minimal risk of contamination and reduced process time. Our specifications regarding tolDC identity and potency allign with the consensus view of the international community of investigators active in the field of tolDC research for negative vaccination. Recently, we received approval from the national competent authorities to test the safety of administering tolDC in patients with MS in a first-in-human clinical trial.
Disclosure: The authors have nothing to disclose.
Abstract: P1193
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
While emerging evidence indicates that dendritic cells play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect of using dendritic cells as disease-modifying therapy. Indeed, since the introduction in the clinic in 1996, the clinical benefit of dendritic cell-based therapy has been well documented in numerous clinical trials in patients with cancer and infectious diseases. More recently, tolerance-inducing or tolerogenic dendritic cells (tolDC) also became a promising immunotherapeutic tool for restoring immune tolerance in several autoimmune diseases including MS. To guarantee utmost patient safety, clinical trials using cell-based medicinal products such as tolDC need to be conducted under stringent good manufacturing practice (GMP) guidelines and regulations defined by the European Union and the US Food and Drug Administration. In line with these rules and regulations, we report here a standardized method for the generation of tolDC according to GMP guidelines. Critical parameters including identity, viability, cell yield and potency were assessed. In doing so, specification limits for the final drug substance were determined using statistical process controls. For this, the results from the qualification batches following the ex vivo tolDC generation protocol were determined. In brief, our results reveal that tolDC display a maturation-resistant phenotype, indicated by a reduction of 35% or more in the upregulation of the expression of costimulatory markers as compared to control DC following cytokine-induced acivation. For functional release, tolDC should induce a reduction of at least 65% in IFN-gamma production by co-cultured T cells as compared to control DC.
In conclusion, a reproducible method for the generation of human tolDC according to GMP guidelines is described with minimal risk of contamination and reduced process time. Our specifications regarding tolDC identity and potency allign with the consensus view of the international community of investigators active in the field of tolDC research for negative vaccination. Recently, we received approval from the national competent authorities to test the safety of administering tolDC in patients with MS in a first-in-human clinical trial.
Disclosure: The authors have nothing to disclose.