The main objective of the HemAcure project is to develop and refine the tools and technologies for a novel ex vivo prepared cell based therapy to treat the bleeding disease haemophilia A (caused by genetic deficiency in clotting factor VIII (FVIII)) that should ultimately lead to improved quality of life of the patients. The concept is a further development of our approach, established during the FP7 ReLiver project led by Medicyte. From the very beginning, we balance two important goals, maximizing the product’s efficacy and safety profile on one side and minimizing production cost on the other by enhancing the product’s manufacturability. HemAcure relates to the work program as we focus on the refinement of all steps and tools of our ex vivo gene therapy approach. These steps involve 1) isolation and culture of cells from patients’ blood, 2) manipulation of patient cells to repair its genetic defect by ex vivo introducing the correct genetic copy of FVIII (mutations in this gene lead to hemophilia A), 3) automation of cell expansion in a novel and passage-less scalable bioreactor, 4) continuously monitoring of cells during and after expansion with respect to their safety profile and functionality, 5) cell implantation into a worldwide unique medical device for targeted delivery of therapeutic Factor VIII and 6) proof-of-concept and safety studies in appropriate haemophilia A animal models. The aim of adapting the proof-of-concept to GMP requires a risk based approach, by means of a clear understanding of the whole process from design to production of the therapeutic cells and a systematic way to identify and prevent risks that are not acceptable for the patient. All steps will be designed and conducted according to European GMP-regulations to ensure that the product will fully comply to the requirements for quality of the European authorities.

Our proposal encompasses parallel clinical trials addressing the feasibility and the effectiveness of donor-derived regulatory T cells (Treg) as a therapeutic agent in the treatment and prevention of tissue and organ damage resulting from graft versus host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). We propose a collaborative clinical study in which Treg therapy for GHVD is the common dominator. However, by bringing together several clinical centers with expertise in this area, we are also having the opportunity to simultaneously address other issues that would not otherwise be addressable by each clinical center on its own. Firstly, by using different Treg preparation strategies, we will be able to determine whether ex vivo isolated Treg are sufficient or whether in vitro expansion and subsequently higher dosages are required. Secondly, we will investigate if sole Treg infusion is effective or if rather co-administration of therapeutic agents that are likely to induce Treg survival and expansion in vivo (rapamycin; IL-2) is required for a successful response to Treg therapy. The studies on GVHD treatment outcome will be pursued together with a detailed analysis of immune monitoring, comprising T cell receptor clonotype tracking and tissue regeneration markers, in order to further understand the mechanisms underlying the therapeutic and regenerative potential of Treg cells. Our consortium has developed a concerted approach to the topic of Treg therapy in GVHD. This is a unique opportunity to determine the validity of this cellular immunotherapy approach in GVHD prevention and treatment, with potential for a significant impact on patient quality of life, survival rate and ultimately on the quality of health care provided.