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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - nTRACK (Multimodal nanoparticles for structural and functional tracking of stem cell therapy on muscle regeneration)

Teaser

Summary

Cell therapy offers promising opportunities to approach several diseases for which no effective therapies are currently available. However, the prognosis of the treatment efficacy commonly only relies on the progression of the disease symptoms. The current lack of methods providing real-time tracking of transplanted cells and knowledge on their early biodistribution and viability, is one of the major weakness of the available cell-based treatments. The main goal of nTRACK is to develop a safe and highly sensitive multimodal nanoimaging agent enabling noninvasive, quantitative and longitudinal stem cell tracking and whole body biodistribution. nTRACK is aimed to provide information on cell (long-term) viability using the combination of CT, MRI and PET, which are imaging modalities that are clinically available. The synthesis of nTRACK NPs and cellular labeling processes are being scaled up and will follow good manufacturing practice (GMP) requirements. The first results coming from scaling up showed challenges and demonstrate the difficult transition from lab to industry. In contrast, the results delivered from in vitro such as the definition of standard operating protocol for cell labelling as well as research on nanoparticle intracellular fate of the nanoparticles and, in vivo models that resembles human lesions, provided encouraging results regarding the safety of the product as well as transplanted cells imaging under CT and PET.
A second goal is to establish a predictive model for early assessment of treatment effectiveness, based on short-term evaluation of the typical migration and biodistribution patterns of the stem cells. This predictive model could substantially improve overall management of the disease and move cell therapy treatment into the so-called precision medicine. From â€œone size fits allâ€™ concept towards personalized treatment. The nTRACK technology will be demonstrated on a muscular injury model that resembles human injuries, using clinical imaging infrastructure commonly used in hospital settings. Another key piece of activity is the non-clinical safety studies on the nTRACK nanoparticles will be conducted following the conclusions of a series of formal interactions with regulatory authorities, to allow the prompt introduction into clinical.
The need of clinical imaging is a requisite for characterizing damaged tissue/organ and for measuring the safety and efficacy of regenerative medicine while the ability to track the fate and function of transplanted cells with current technologies is still unsolved according to the technology and IPR monitoring performed during this period. Thus, nTRACK project could be placed in the front edge of nanolabelling stem cells that will contribute to the innovation, competitiveness, growth improvement of EU and other territories.
Itâ€™s worth to highlight the milestone reached in terms of product definition according to the regulatory framework. Though the consortium assumed that the definition of the nTRACK product would be an easy task, it has been confirmed right after the very first meeting. To sort this out, multiple actions have been performed to reach a proper product definition. These action ended up in a meeting with the Innovation Task Force at the EMA where it was exposed the border line nature of this technology. Besides, nTRACK consortium become member of the the committee CT-TRACS(Cell Therapy - TRAcking, Circulation, & Safety) of the HESI (Health and Environmental Sciences Institute) which confirmed the uniqueness of the nTRACKâ€™s technology: the existence of a regulatory gap to define this type of products as a medicinal drug or medical device. Further work will be done to assess the effect of nTRACK on EU policies, regulations and standardization of this kind of technology. Consequently, if nTRACK succeeds it will be opening of a new market sector for imaging equipment and supplies, reinforcement of the European healthcare supply chain and improveme

Work performed

The main results generated this first period of activity are listed:
- Technology transfer of nanoparticles synthesis from lab-scale to GMP-grade industrial scale
- Established a SOP for radiolabelling the lab-scale nanoparticles as well as PET imaging assays have been done
- Ongoing upscaling nTRACK NPs, SOPs for manufacturing conditions, in process control and implementation of the quality management system for complying with GMP requirements
- SOP for staining PLX-PAD cells with nTRACK-NPs
- Itâ€™s been defined the primary purpose of the nTRACK nanoparticles should be â€œthe tracking of cell therapy with labelled stem cells to be used during development (non-clinical and clinical) of new cell therapies.

Final results

The progress beyond the state of the art set at the beginning of the project is being reached according to the activities performed during this period of activities:
- Precisely tune and control the chemical and physical properties of contrast nanomaterials to enhance strength the sensitivity. A exhaustive list of characterization assays has been established: biological, physico-chemical and imaging.
- Correlation of intracellular fate and nTRACK NP effectiveness as contrast agents. First hints of the intracellular trafficking has been identified.
- A system to assess cellular dynamics, cellular kinetics (homing, migration) and efficacy. Multimodal contrast agents, along with a dedicated novel imaging analysis concept, will be able to provide clinically relevant structural and functional information.
- Advanced predictive model for early assessment of cell therapy effectiveness, based on easy-to collect data. Prediction lesion models have been developed as well as computational models to predict transplanted cells behavior is being developed.
- Progress in medical regulatory guidance for the development of nanotechnology-based imaging approaches transplants. nTRACK is strongly contributing to this progress by close contact with the regulatory authorities and non-governmental associations.
The progress beyond the state of the art to be reached by the project activities will be the ground to tackle the socio-economic challenges faced by EU such as the progress of the regenerative medicine and such progress will impact on the healthcare systems improving patient outcome as well as reduction of drug expenditure; to expand nanomedicine market, the adaptability of nTRACK technology has the potential to exploit diverse market opportunities, which makes the nTRACK concept very attractive from the cost/revenue point of view. nTRACK could not only impact the imaging diagnostic agents market and the nanomedicine market, but also the expansive and growing market of regenerative medicine and associated industry; improvement in innovation capacity and integration of new knowledge to foster novel companies. nTRACK technology encloses the adaptation of this technology to other clinical indications requiring cell-based therapies (cardiac, immunological diseases, autoimmune diseases, brain degenerative diseases, trauma, etc), and customized functionalized NPs to be used as novel contrast or therapeutic agents. The innovative nature of nTRACK concept goes beyond the cell transplant tracking system and has the potential to impact the growing network of interdisciplinary companies of the regenerative industry.