The Biomarkers and Precision Medicine Unit of IIS La Fe successfully validates advanced technologies for personalized cell therapies in SMARTER

Over the course of 3 years, SMARTER aimed to optimize the production of advanced therapies based on the patient's own cells, such as tumor-infiltrating lymphocytes (TILs), used in the treatment of certain types of cancer (e.g., lung cancer and melanoma). These therapies present significant challenges related to their technical complexity, costs, and manufacturing times, and are heavily influenced by the biological properties of the starting material, that is, how the TILs are isolated from the patient.

In the first phase of the project, the consortium managed to identify metabolic biomarkers associated with the production process of the TIL-based cell therapy. A second phase, building on the identified biomarkers and modifiable culture conditions, identified critical parameters that could improve the reproducibility and quality of the final product.

Once the processes to control were identified, advanced monitoring technologies-such as Raman spectroscopy sensors and 2D fluorescence-were integrated into dynamic bioreactors, allowing real-time tracking of the cell expansion process and the monitoring of nutrients consumed and metabolic products released by the TILs into the medium. Additionally, based on the monitoring of these parameters, an advanced process control system was integrated to ensure optimal nutrient concentrations throughout the entire cell production process.

At the experimental level, the consortium succeeded in optimizing the manufacturing conditions, reducing the total process time by approximately four days without compromising the quality standards required for clinical application. Finally, the project culminated with the validation of the developed strategies using material from real patients, confirming their viability in a clinical environment and solidifying the robustness of the results obtained.

The role of IIS La Fe in the SMARTER project
The Biomarkers and Precision Medicine Unit, with its extensive experience in biomarker identification and T-cell metabolism, played a key role in identifying the metabolic biomarkers and defining the critical parameters to monitor and control to optimize the TIL production process. Due to the characteristics of the measurement instruments implemented within the bioreactors, the UBMP researchers played a crucial role in validating, through quantitative analyses based on liquid chromatography coupled with mass spectrometry, the estimated concentrations obtained from real-time monitoring of the key process parameters.

IIS La Fe's participation allowed for the validation that the technological solutions designed-including the advanced monitoring systems and bioprocess control systems-are applicable in real-world conditions beyond the experimental environment. This clinical validation is a crucial step to guarantee the viability, safety, and robustness of the new intelligent manufacturing models for cell therapies.

The conclusions of the project reinforce the potential of smart manufacturing technologies to improve the efficiency, scalability, and sustainability of advanced cell therapies. Furthermore, they lay the groundwork for enabling safer and more effective access to personalized treatments in oncology, bringing technological innovation closer to real clinical practice.

Budget and consortium
SMARTER received €4 million in funding from Horizon Europe, the EU's research and innovation framework program for 2021-2027. Among other aspects, it promotes the competitiveness and growth of the EU. The program facilitates collaboration and strengthens the impact of research and innovation in the development, support, and implementation of EU policies while addressing global challenges.

To carry out this project, a consortium of partners was assembled, including the Biomarkers and Precision Medicine Unit of IIS La Fe, with extensive experience in discovering metabolic biomarkers. The consortium, initially led by the biopharmaceutical company Achilles Therapeutics (UK), includes the Leibniz University of Hannover (Germany), experts in advanced sensor development, and Cell and Gene Therapy Catapult (UK), an independent organization committed to advancing cell therapies.