A FACTT General Benefits

A FACTT – The benefits of a European network on Cell Based Tolerance-inducing Therapies

Reasons for A FACTT Action

Cells with tolerogenic function (e.g. tolAPC and Tregs) have become a promising immunotherapeutic tool to treat AID, severe allergies, or to improve transplantation outcomes. The main advantage of CTT over current available therapies is that they have the potential to restore the underlying problem long-term without compromising protective immunity. After 15 years of intense research, these cellular therapies have recently entered the stage of clinical trials. However, the lack of standardised and validated protocols to compare the tolerogenicity of the cellular products and for immune monitoring of patients makes it difficult to compare individual trials, decelerating the potential progress of the CTT field.

A FACTT: how to achieve the objective

The objective of the A FACTT Action is to focus and accelerate the field by setting up standardised protocols between different centres, allowing for comparisons between CTT products and trial outcomes. In particular, comparative functional parameters (‘tolerogenicity’) and safety of CTT products will be defined and validated. Furthermore, protocols for immune monitoring of CTT application to patients will be standardised and implemented in clinical trials.

The expected result is that the implementation of these standardised protocols will allow for the comparison between different CTT products and the outcomes of CTT trials, helping to answer important outstanding questions, including ‘which type of CTT is best for a certain disease’, and ‘how best to produce these cells’.

The only way to achieve this objective is to build a network of CTT experts. Due to the specialised nature of the field, relatively few groups are conducting CTT in Europe and world-wide. Therefore, there is a very strong need for a network of experts at European level.

Short-term and long-term benefits of A FACTT

The short-term benefits of A FACTT will be that through the standardisation of protocols to measure CTT functionality and trial outcome, the efforts of different groups can be combined, avoiding redundancy and increasing the power of CTT studies. Thus, A FACTT will allow for more cost effective and comparable research and clinical trial data to be generated within the network. This will lead to a better understanding of the MoA of CTT, greatly accelerating implementation of CTT in the clinic. In addition, the Action will lead to improved dissemination of knowledge to interested parties, including the pharmaceutical industry, the public and regulatory authorities. It will also help the training and mobility of Early-Stage Researchers (ESR), and will result in the submission of grant proposals for further multi-centre trials.

The long-term benefits of A FACTT will be that it will minimise the adverse effects of treatment on patients, rendering the life-long treatment with immunosuppressive drugs obsolete. Furthermore, because CTT-based therapies are well suited for individualised therapeutic approaches, they have curative potential for some of these diseases.

Finally, by improving patient health and well-being, CTT can reduce the economic burden of chronic and debilitating diseases in Europe and the rest of the world.

Who will benefit from A FACTT?

The outcomes of A FACTT are both benefits at the scientific and societal/economic level. This Action is aimed at advancing the scientific and medical expertise within the CTT field, and to enhance quality of life of patients and the society by improving therapies for several debilitating diseases and conditions. Although Europe, together with the USA, is at the forefront of CTT, more could be done to solidify Europe’s role as a major player in this field. By setting up and leading this network (which will also be open to CTT groups outside of Europe), European groups will improve their expertise in all aspects of developing and clinically implementing CTT, making them more visible and attractive for high quality researchers and clinicians to join their groups.

Complementarity with other research programmes

A FACTT is complementary to other national and EU-wide activities on CTT, as each of the other activities focus on a specific cell type or a specific patient group, like the FP7 “ONE Study” that uses CTT as prophylaxis of kidney transplant rejection. A FACTT will develop standardised immune monitoring protocols and consensus parameters to support the systematic development of CTT-based clinical trials with different cells in all clinical fields and to identify general tolerance signatures, Correlates of Protection (COP) and biomarkers for the different CTT approaches. This immunomonitoring will be complementary to the one of COST Action BM0907 “European Network for Translational Immunology Research and Education (ENTIRE): from immunomonitoring to personalised immunotherapy” in which multiparametric analysis of a big panel of immunological parameters in healthy donors will provide reference of the normal “immunotype”.

A FACTT is the first European initiative to bring together different disciplines in the context of human immune tolerance

Well-coordinated efforts will also limit overlap and render the CTT field more efficient and cost-effective. This is the first European initiative to bring together different disciplines in the context of human immune tolerance with the main objective to accelerate and improve the clinical efforts towards CTT and, at the same time, employ CTT-based trials as important experiments to develop a better understanding of immune tolerance in different disease contexts.

It is of utmost relevance to integrate experiences from researchers and experts specialised in different tolerance-inducing cell types and clinical fields. In the USA, the Immune Tolerance Network (ITN), although not focused on CTT, is established to pursue similar aims. A FACTT, made possible by the COST Action, may be a first start to set up the European counterpart and simultaneously create a bridge with the ITN to exchange mechanistic and clinical insights and protocols. The Action is timely as the European Medicines Agency (EMA) is still consulting on novel acts that will include advanced therapy medicinal products such as tolAPC and Tregs.

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