Enhancing cell therapies with genomic techniques

Expected Outcome:

This topic aims at supporting activities that are enabling or contributing to one or several expected impacts of destination “Developing and using new tools, technologies and digital solutions for a healthy society”. To that end, proposals under this topic should aim to deliver results directed towards and contributing to several of the following expected outcomes:

• Biomedical scientists dispose of tools that allow them to engineer cells with specific therapeutic features.
• Improved methods and assays are available for biopharmaceutical developers.
• Clinicians will get access to innovative therapeutic approaches enabling them to treat conditions, where there are currently no or only insufficient therapeutic strategies.
• Cell engineering will be enriched and pave the way for novel personalised therapy options.

Scope:

Therapies based on cells, stem cells or somatic cells, have been shown to be highly effective as therapeutics for a variety of health conditions. However, bottlenecks remain which currently hamper their safe and efficient application on a large scale. Genome- and epigenome editing have great potential to overcome some of these bottlenecks and to lead to the next-generation of cell-based therapies. Advancing the frontier of cell-based therapy with these tools and further translation of such research into clinically viable solutions may open up a new era of innovative therapies.

This topic aims at the design of engineered cells to address the current limitations of cellular therapies, such as delivery efficiency, patient safety, in vivo persistence, desired therapeutic effect, immune tolerance and manufacturing workflows. The chosen approach should enable to control the characteristics, fate and function of the engineered cells from gene level onwards and thus lead to customised cells with improved therapeutic features.

The use of genetic engineering and in particular gene editing tools should be a key element in the design of the engineered cells. The therapeutic action should be based on the endogenous capabilities of the cells; the exogenous loading of cells with drugs (using the cells as drug carrier) is not in scope.

The engineered cells should be derived from human cells. Either stem cells or somatic cells may be used, but of allogeneic origin, thereby opening up the development of “off-the-shelf” cell therapeutics.

Applicants should explicitly state in their proposal which of the following therapeutic areas is targeted and the proposed work should address only this specific therapeutic area:

1. Cancer and oncology
2. Nervous and sensory system
3. Cardiovascular and circulatory system
4. Endocrinology and metabolic system
5. Musculoskeletal system
6. Digestive system
7. Infectious diseases
8. Respiratory system
9. Dermatology
10. Immune system and auto-immune diseases
11. Other

The activities should comprise all the following elements:

• Engineering of synthetic genetic circuits acting as switches to modulate the desired function(s) and their integration in the chosen cells, with the help of new genomic techniques. Next to new genomic techniques like genome and epigenome editing, also synthetic biology introducing transgenes or artificial genes may be used to endow the engineered cells with improved therapeutic properties and achieve the desired cell phenotype. The applicants should use gene control systems, including transcriptional, translational and/or post-translational control, or other approaches which install on-off switches and control systems, like e.g. a “sense-and-respond” mechanism in the engineered cells, sometimes also referred to as “theranostic cells”.
• For the efficient construction and acceleration of the design-build-test cycles of the engineered cells containing the programmed functionalities state of the art tools including digital ones (e.g. Computer-Aided Design - CAD - and similar tools) should be used.
• Suitable in-vitro and ex-vivo systems should be used for testing and demonstration of function and performance of the engineered cells. Their added value, safety and efficacy should be ensured in appropriate pre-clinical models for one specific therapeutic area. Any disease, dysfunction or health impairment may be selected as therapeutic area.
• Applicants should show that the engineered cells are safe and exert the desired therapeutic effect in-vivo. Engagement and interaction with regulatory authorities during the project is essential for qualification of the developed cell-based therapy and in view of the conduct of clinical studies. The demonstration of the feasibility of the proposed cell-based therapy in first in-human studies would be an asset.

Sex differences should be taken into consideration, both with regard to the parent cells and for the targeted therapeutic application. Collaboration with relevant European research infrastructures and findings from EU-supported research projects should be considered. Participation of small and medium-sized enterprises (SMEs) is strongly encouraged.

Proposals should consider the involvement of the European Commission's Joint Research Centre (JRC) as a potential interface between research activities and pre-normative regulatory science and in relation to the potential validation of test methods fit for regulatory purpose. In that respect, the JRC will consider collaborating with any successful proposal and this collaboration, when relevant, should be established after the proposal’s approval.

Applicants should provide details of their clinical studies^[1] in the dedicated annex using the template provided in the submission system. As proposals under this topic are expected to include clinical studies, the use of the template is strongly encouraged.

[1] Please note that the definition of clinical studies (see introduction to this work programme part) is broad and it is recommended that you review it thoroughly before submitting your application.