Contributions
Abstract: P1202
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Treatment options for multiple sclerosis (MS) have exponentially increased in the past decade. However, higher treatment efficacy brings treatment-related risks due to reduced immune competence. Hence, an unmet need for safer and more selective treatments targeted towards the cause of the disease remains. In this respect, antigen-specific tolerization with autologous tolerogenic dendritic cells (tolDC) is a promising approach.
Objectives: To assess the clinical use of tolDC in a well-defined population of MS patients in two single-center clinical trials, comparing two ways of tolDC administration, namely intradermal (i.d.) (MS-tolDC, Antwerp) and intranodal (i.n.) (TOLERVIT-MS, Badalona).
Aims: To demonstrate safety and feasibility of therapeutic use of tolDC in MS patients.
Methods: Via a leukapheresis procedure, autologous monocytes are extracted. These are cultured in GMP-grade cell culture medium supplemented with 2% human AB serum, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and 1α,25 dihydroxyvitamin D3. At day 4, tolDC are stimulated using an inflammatory cytokine cocktail. At day 6, tolDC are harvested, loaded with 7 myelin antigens (MBP13-32, MBP111-129, MBP154-170, PLP139-154, MOG1-20, MOG35-55 and MBP83-99), and cryopreserved. Six administrations at consecutive intervals are planned in 3 cohorts receiving incremental doses of tolDC either i.d. or i.n., according to a best-of-five design. For safety, the number of adverse events and relapses, neurological disability, and magnetic resonance imaging (MRI) endpoints will be assessed. Immunological monitoring is performed and quality of life is monitored. Results: To date (May 15th 2018), 3 patients were enrolled in the clinical trial in Antwerp. Two of three are currently in the treatment phase of the clinical study and safety is continuously being monitored. For the third patient, the cell product failed to fulfill the release criteria and the product was destroyed. 3 patients are in screening. In Badalona, 5 patients are recruited in the clinical trial. For 2 patients, the cell product failed to fulfill the prespecified release criteria and was not administered. In 3 patients the cells fulfilled the release criteria and are ready for injection. Safety data will be reported.
Conclusions: We describe interim results of the MS-tolDC and TOLERVIT-MS studies and assess the safety and feasibility of the first dose cohort.
Disclosure: Barbara Willekens received travel support for attending meetings from Biogen, Merck Serono, Genzyme, Roche, TEVA. The institution received research support from Sanofi-Genzyme and Roche and speaker and consultancy honoraria from Roche, Biogen, Merck, Novartis, Sanofi-Genzyme, TEVA. She is supported by a research fellowship (2016-2018) of the University of Antwerp to work on this project.
Judith Derdelinckx holds a PhD fellowship from the Research Foundation-Flanders (FWO). Catharina C. Gross received speaker honoraria and travel expenses for attending meetings from Biogen, Euroimmun, Genzyme, and Bayer Health Care. Her work is funded by the German Ministry for Education and Research (BMBF; 01GI1603A), the German Research Foundation (DFG; GR3946/3-1 and SFB/Transregio 128 A09), and the European Union (Horizon2020, RESTORE). Heinz Wiendl received honoraria for scientific advisory boards/steering committees from Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, and Sanofi-Genzyme. He received speaker honoraria and travel support for attending meetings from Actelion, Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Lundbeck, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Globa. HW received compensation as a consultant from Abbvie, Actelion, Biogen, Immunic AG, Novartis, Roche, RxMx, and Sanofi-Genzyme. He also received research support from the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, European Union, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, RE Children's Foundation, PML Consortium, Swiss MS Society, Biogen GmbH, GlaxoSmithKline GmbH, Roche Pharma AG, and Sanofi-Genzyme. The institution of Zwi Berneman received research support from Roche and Sanofi-Genzyme. The other authors report no disclosures.
Funding source: This work was supported by the Methusalem Funding Program from the University of Antwerp, by an applied biomedical research project of the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-TBM 140191), project PI14/01811, integrated in the Plan Nacional de I+D+I and co-supported by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III from Spain, Convocatoria AES 2016 and by the Belgian Charcot Foundation. Furthermore, the authors received funding from the European Union´s Horizon 2020 research and innovation program under grant agreement number 779316.
Trial registration: Both studies are registered at clinicaltrials.gov: NCT02618902 and NCT02903537 (EudraCT numbers: 2015-002975-16 and 2015-003541-26, respectively).
Abstract: P1202
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Treatment options for multiple sclerosis (MS) have exponentially increased in the past decade. However, higher treatment efficacy brings treatment-related risks due to reduced immune competence. Hence, an unmet need for safer and more selective treatments targeted towards the cause of the disease remains. In this respect, antigen-specific tolerization with autologous tolerogenic dendritic cells (tolDC) is a promising approach.
Objectives: To assess the clinical use of tolDC in a well-defined population of MS patients in two single-center clinical trials, comparing two ways of tolDC administration, namely intradermal (i.d.) (MS-tolDC, Antwerp) and intranodal (i.n.) (TOLERVIT-MS, Badalona).
Aims: To demonstrate safety and feasibility of therapeutic use of tolDC in MS patients.
Methods: Via a leukapheresis procedure, autologous monocytes are extracted. These are cultured in GMP-grade cell culture medium supplemented with 2% human AB serum, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and 1α,25 dihydroxyvitamin D3. At day 4, tolDC are stimulated using an inflammatory cytokine cocktail. At day 6, tolDC are harvested, loaded with 7 myelin antigens (MBP13-32, MBP111-129, MBP154-170, PLP139-154, MOG1-20, MOG35-55 and MBP83-99), and cryopreserved. Six administrations at consecutive intervals are planned in 3 cohorts receiving incremental doses of tolDC either i.d. or i.n., according to a best-of-five design. For safety, the number of adverse events and relapses, neurological disability, and magnetic resonance imaging (MRI) endpoints will be assessed. Immunological monitoring is performed and quality of life is monitored. Results: To date (May 15th 2018), 3 patients were enrolled in the clinical trial in Antwerp. Two of three are currently in the treatment phase of the clinical study and safety is continuously being monitored. For the third patient, the cell product failed to fulfill the release criteria and the product was destroyed. 3 patients are in screening. In Badalona, 5 patients are recruited in the clinical trial. For 2 patients, the cell product failed to fulfill the prespecified release criteria and was not administered. In 3 patients the cells fulfilled the release criteria and are ready for injection. Safety data will be reported.
Conclusions: We describe interim results of the MS-tolDC and TOLERVIT-MS studies and assess the safety and feasibility of the first dose cohort.
Disclosure: Barbara Willekens received travel support for attending meetings from Biogen, Merck Serono, Genzyme, Roche, TEVA. The institution received research support from Sanofi-Genzyme and Roche and speaker and consultancy honoraria from Roche, Biogen, Merck, Novartis, Sanofi-Genzyme, TEVA. She is supported by a research fellowship (2016-2018) of the University of Antwerp to work on this project.
Judith Derdelinckx holds a PhD fellowship from the Research Foundation-Flanders (FWO). Catharina C. Gross received speaker honoraria and travel expenses for attending meetings from Biogen, Euroimmun, Genzyme, and Bayer Health Care. Her work is funded by the German Ministry for Education and Research (BMBF; 01GI1603A), the German Research Foundation (DFG; GR3946/3-1 and SFB/Transregio 128 A09), and the European Union (Horizon2020, RESTORE). Heinz Wiendl received honoraria for scientific advisory boards/steering committees from Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, and Sanofi-Genzyme. He received speaker honoraria and travel support for attending meetings from Actelion, Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Lundbeck, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Globa. HW received compensation as a consultant from Abbvie, Actelion, Biogen, Immunic AG, Novartis, Roche, RxMx, and Sanofi-Genzyme. He also received research support from the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, European Union, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, RE Children's Foundation, PML Consortium, Swiss MS Society, Biogen GmbH, GlaxoSmithKline GmbH, Roche Pharma AG, and Sanofi-Genzyme. The institution of Zwi Berneman received research support from Roche and Sanofi-Genzyme. The other authors report no disclosures.
Funding source: This work was supported by the Methusalem Funding Program from the University of Antwerp, by an applied biomedical research project of the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-TBM 140191), project PI14/01811, integrated in the Plan Nacional de I+D+I and co-supported by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III from Spain, Convocatoria AES 2016 and by the Belgian Charcot Foundation. Furthermore, the authors received funding from the European Union´s Horizon 2020 research and innovation program under grant agreement number 779316.
Trial registration: Both studies are registered at clinicaltrials.gov: NCT02618902 and NCT02903537 (EudraCT numbers: 2015-002975-16 and 2015-003541-26, respectively).