Periodic Reporting for period 1 - InnoCAR-T (Innovative design and implementation of next-generation Point-of-Care CAR-T)
Reporting period: 2023-01-01 to 2024-12-31
Chimeric Antigen Receptor (CAR) T-cells (CAR-Ts) have emerged as a key breakthrough in the treatment of B-cell malignancies, with long term remission and cure in previously end-stage patients. These unprecedented clinical responses have clearly transformed the clinical landscape, with several commercial CAR-T products being available as standard-of-care in EU countries.
However, the current commercial production paradigm by pharmaceutical companies poses significant challenges to rapid implementation. Specifically, products have long lead times, thereby, precluding severely ill patients from eligibility for this life-saving therapy. Further, centralized production poses challenges to rapid innovation and has significant environmental impact. Moreover, such centralized production of commercial CAR-T products has prohibitively high costs that strain the healthcare systems in Europe, even in the currently limited indication areas for which it is approved. Indeed, some countries do not include CAR-Ts in their public standard-of-care. Therefore, efforts currently focus on development of academic point-of-care (PoC) production as alternative, which is also the primary focus of InnoCAR-T.
Furthermore, even for the successful story of B cell lymphoma long-term clinical responses are restricted to ~50% of patients, whereas for most other types of cancers clear CAR-T breakthroughs are still lacking. This is due to additional challenges that need to be overcome for effective CAR-T therapy, including tumour micro-environmental immunosuppression that results in the shut-down of CAR-T in the tumour lesion.
InnoCAR-T’s science objective is to use breakthrough science to develop next-generation academic CAR-T products that aim to address these bottlenecks and deliver curative CAR-T-based tumour immunity with optimal and affordable care. Specifically, we will 1. develop flexible, scalable and rapid CAR-T manufacturing capacity for academia and 2. develop various immunomodulatory therapeutic approaches for the design of next-generation CAR-T formulations to overcome immunosuppression.
With these advances, InnoCAR-T aims to drive the implementation of PoC CAR-T therapy in Europe.
However, the current commercial production paradigm by pharmaceutical companies poses significant challenges to rapid implementation. Specifically, products have long lead times, thereby, precluding severely ill patients from eligibility for this life-saving therapy. Further, centralized production poses challenges to rapid innovation and has significant environmental impact. Moreover, such centralized production of commercial CAR-T products has prohibitively high costs that strain the healthcare systems in Europe, even in the currently limited indication areas for which it is approved. Indeed, some countries do not include CAR-Ts in their public standard-of-care. Therefore, efforts currently focus on development of academic point-of-care (PoC) production as alternative, which is also the primary focus of InnoCAR-T.
Furthermore, even for the successful story of B cell lymphoma long-term clinical responses are restricted to ~50% of patients, whereas for most other types of cancers clear CAR-T breakthroughs are still lacking. This is due to additional challenges that need to be overcome for effective CAR-T therapy, including tumour micro-environmental immunosuppression that results in the shut-down of CAR-T in the tumour lesion.
InnoCAR-T’s science objective is to use breakthrough science to develop next-generation academic CAR-T products that aim to address these bottlenecks and deliver curative CAR-T-based tumour immunity with optimal and affordable care. Specifically, we will 1. develop flexible, scalable and rapid CAR-T manufacturing capacity for academia and 2. develop various immunomodulatory therapeutic approaches for the design of next-generation CAR-T formulations to overcome immunosuppression.
With these advances, InnoCAR-T aims to drive the implementation of PoC CAR-T therapy in Europe.
In the past project period, all 10 DCs have been recruited (from March 2023 to Jan 2024) and have started the scientific work on both PoC manufacturing solutions and next-gen CAR-T cell development. In view of the short period, the advances made by the DCs in their individual projects have not yet been published in peer-reviewed journals, but several presentations have been held at international conferences such as the EHA-EBMT 6th and 7th CAR-T meetings as well as the ISCT 2025 Conference. Within each individual research project, important proof-of-concept data has been successfully generated by the DCs and the work progresses according to schedule, with several manuscripts being prepared for publication in the near future.
At this early stage of the project, no completed, published and sharable results are available yet. In line with the program, all DC projects are focused on concepts designed to move PoC CAR-T beyond the state of the art.