Dr Diego Leon-Rico, representing SCIDNET Partner GOSH (Great Ormond Street Hospital), presented a poster in the annual European Society of Gene & Cell Therapy Congress (Barcelona, 22-25 October 2019). Below, follows a summary of the poster.

Manufacture of an ATMP for the treatment of X-linked Severe Combined Immunodeficiency (X-SCID)

D Leon-Rico, J W Schott,  E Armenteros-Monterroso, K F Buckland, A Diasakou, I Pereira  C B Ferreira, A Cavazza, K L Shaw, M Armant, D B Kohn, S Y Pai, A J Thasher, C Booth

1: UCL GOS Institute of Child Health, 2: Great Ormond Street Hospital for Children NHS Foundation Trust, 3: U.C.L.A.,  4: Boston Children’s Hospital, 5: Hannover Medical School   

X-SCID is a primary immunodeficiency characterised by the absence of T, B and NK cells. Patients with X1-SCID suffer from recurrent and life-threatening infections. Currently, the only curative treatment is haematopoietic stem cell transplant (HSCT). Previous ex-vivo gene therapy clinical trials have been conducted for this disease, using both gamma retroviral vectors (g-RV) and self-inactivating (SIN) g-RV. However, numerous clinical trials for many diseases, including X-SCID have moved to the use of SIN-lentiviral vectors (LVs). Great Ormond Street Hospital is one of the sites for this clinical trial. Here we describe the optimised 3-day manufacturing procedure consisting of several steps: CD34+ selection using COBE and CliniMACS®Plus from the starting material (mobilised peripheral blood stem cells or bone marrow), pre-stimulation culture in the presence of SCF, FLT3L and TPO cytokines, transduction with a SIN LV where the expression of the therapeutic transgene is driven by the EFS promoter, and a final harvest / formulation process where the transduced cells are resuspended in a commercially available freezing mix and transferred to cryobags. Finally, the cells are cryopreserved using a control rate freezer and stored at LN2 vapour phase. Required QC tests are performed both pre-freeze and post-thaw. The introduction of transduction enhancers (LentiBOOST™ and Protamine sulphate) allows the use of 4-times less vector whilst still achieving enhanced transduction efficiency. A stability study using healthy donor cells has been also conducted demonstrating that the cryopreserved transduced cells are stable for at least 6 months in LN2 vapour phase.

This is the link to the meeting website:

https://www.esgct.eu/Congress/Barcelona-2019.aspx

Prof Axel Schambach (Institute of Experimental Haematology, Hannover Medical School/MHH), in collaboration with Prof Toni Cathomen (Institute for Transfusion Medicine & Gene Therapy, Universitätsklinikum Freiburg), Boris Fehse (University Hospital Hamburg-Eppendorf), Hildegard Büning (MHH) and Ulrich Hacker (MHH, University Hospital Leipzig) co-organized a ‘School Day’ for two hundred (200) High School Students, from eleven (11) classes, from Saxony region in Germany. The presentation took place on the 16^th of September 2019 in University of Leipzig premises, in Leipzig, Germany.

The aim was to introduce students into “gene taxis” to treat immunodeficiencies (presentation by Axel Schambach) and also novel gene therapy options using tailored genome editing (presentation by Toni Cathomen, who is also leader of SCIDNET’s Work Package 5 – Advanced vector technologies and gene editing for SCID). The presentation was considered an excellent opportunity for topics of the SCIDNET Consortium to extend its reach from a purely scientific audience to a wider audience, such as high school students (girls and boys). The final goal was twofold: To inform students of the gene therapy developments and opportunities, not only from a purely research perspective, but also in relation to the exciting career perspectives gene therapy can offer to young scientists.

IPOPI (International Patient Organisation for Primary Immunodeficiencies), a SCIDNET Project Partner, disseminated information about the project at the Immune Deficiency Foundation´s conference in Washington DC (The U.S.), 20-22 June 2019. Johan Prevot, IPOPI Executive Director, had the chance to share project developments with PID patients and other stakeholders from all over the U.S.

Beyond this IPOPI President Martine Pergent engaged in similar activities and shared project developments in her presentation during the IPOPI regional African PID patients meeting, organised back to back to the African Society for Immunodeficiencies (ASID) congress in Dakar (Senegal), 11-12 April 2019.

Link ASID congress, website: http://www.asid-africa.org/en/ program: http://www.asid-africa.org/images/2019/6thAISD_Scientific_Program.pdf

Professor Persis Amrolia (University College London) presented a talk entitled “Antibody-based conditioning for SCT and Gene Therapy” at the 10th Stem Cell Clonality and Genome Stability Retreat on 15^th May 2018.  The oral presentation was given in the “Antibody-based conditioning in allogeneic transplantation” session chaired by Professors Bobby Gaspar (University College London) and Sun-Yung Pai.

Professor Amrolia discussed the outcomes and challenges of a phase 1/2 study using antibody-based minimal intensity conditioning in paediatric patients with primary immunodeficiencies undergoing stem cell transplant.  Professor Amrolia highlighted need to develop more effective antibody-based conditioning agents particularly for immune competent patients and discussed his research team’s approach to the generation and evaluation of novel antibody-based conditioning agents.

Weblink to event and program: https://www.eventbrite.com/e/10th-stem-cell-clonality-and-genome-stability-retreat-tickets-40185696500#

SCIDNET data will be presented at 5th Annual Genome Editing Congress, which will take place on the 7th & 8th of November 2019, in London. SCIDNET Consortium will be represented by Prof Toni Cathomen, from the Institute for Transfustion Medicine & Gene Therapy, Universitätsklinikums Freiburg.

T-cells represent valuable tools for treatment of cancers, infectious or inherited diseases but they are mainly short-lived in vivo.  T-cell therapies would strongly benefit from gene transfer into long-lived persisting naive T cells or T-cell progenitors. During the ASGCT 2019 congress (Washington 2019), INSERM partner presented latest published data on the generation of efficient gene-corrected T-cell progenitors from SCID patients.

https://www.inserm.fr/

https://annualmeeting.asgct.org/am19/

Leiden University Medical Centre (LUMC) hosted SCIDNET 4th Annual Meeting in Netherlands, on 8-9 April, 2019.

Partners had the chance to discuss in detail the progress  per Work Package, at it always is the case in such important meetings. In the context of the project, 3 clinical trials are envisaged (ADA-SCID, SCID-X1, Artemis) and the Consortium reviewed the progress of the respective deliverables and milestones for each trial. It was also important to review all management aspects of the project and finalise all pending issues, related to the 2nd Official Periodic Report (already submitted to the European Commission).

SCIDNET Executive and Scientific Advisory Board Meetings also took place at the end of the 1st day of the meeting, in order to plan for the project’s next steps.

Partners were very satisfied by the extent of analysis and discussion on complex project issues during the meeting, as well as the excellent venue and hospitality of the meeting organisers.

SCIDNET 3rd Annual Meeting took place in London (United Kingdom), on 9-10 April, 2018.

Partners had the chance to discuss in depth the progress, achievements, challenges, successes and lessons learned in each Work Package. This was necessary in view also of the preparation of the 2nd Periodic Report to the EU Commission (due in February 2019).

The aforementioned discussions above provided useful feedback for both SCIDNET Executive and Scientific Advisory Boards’ Meetings, which also took place during the 2-day meeting.

SCIDNET project is privileged to have world-recognised academics and researchers, not only in its Executive Board, but also in its Scientific Advisory Board (SAB). The feedback received in writing (in the form of minutes) from SAB members, is highly desirable and is taken into account for the continuation of project activities.

The 2016 Annual Meeting of American Society of Gene and Cell Therapy (ASGCT) took place on May 4-7, 2016, in Washington. The meeting featured ground breaking clinical trial results, cutting edge technology advancements, and social networking events.

Several SCIDNET partners attended and presented at the conference including:

• SCIDNET Coordinator Prof Bobby Gaspar – Chair of Education session on Orphan Diseases
• Prof Fulvio Mavilio – Lecture entitled “De-risking Gene Therapy for Rare Diseases: The Role of Non-profit Research Organizations”
• Dr Karin Pike – Lecture entitled “Hematologic & Immunologic Diseases I”
• Ian Johnston, PhD – Chair of Tools and Technology Forum during Poster Session II
• Prof Axel Schambach, participated in International Committee and on the Retroviral Vectors Abstract Review Board
• Dr Emmanuelle Six, lecture entitled “Generation of functional regulatory T cells by FOXP3 gene transfer into CD4 T cell from IPEX patients”

The American Society of Gene & Cell Therapy is the primary professional membership organization for gene and cell therapy. The Society’s members are scientists, physicians, patient advocates, and other professionals. The mission of the ASGCT is to advance knowledge, awareness, and education leading to the discovery and clinical application of genetic and cellular therapies to alleviate human disease.

For the consortium, ASGCT was a great opportunity to engage with industry professionals and patients about an exciting and fast-developing area of clinical research and disseminate the SCIDNET project.