Periodic Reporting for period 2 - T2EVOLVE (Accelerating Development and Improving Access to CAR and TCR-engineered T cell therapy)
Berichtszeitraum: 2022-01-01 bis 2023-06-30
Engineered chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cells are a transformative new form of therapy that involves removing immune cells from patients with cancer, modifying them so that they are better able to find and fight cancer.
A number of challenges arise because engineered cell therapy is a complex therapeutic approach that works by modifying complex systems within the body. The field needs better models to predict which new therapies will be successful, standards for processes, improved regulations, better awareness of engineered cell therapy and the barriers to access.
To reduce the barriers that are slowing down the development and are limiting access to engineered T cell therapies in Europe, the T2EVOLVE consortium will seek to achieve 6 central objectives:
1. Optimization of pre-clinical (laboratory) models, tools, and pharmacodynamic (PD) markers to better predict toxicity and efficacy of engineered T cell therapies before they enter clinical trials.
2. Definition of gold standard analytical methods pre- and post-T-cell infusion and harmonization of product characterization, release testing, monitoring, long-term (e.g. genomic safety) assessment, to enable inter-product comparability, value attribution, and the development of sustainable reimbursement.
3. Selection of optimal lymphodepletion regimens (pre-treatment chemotherapy) by drawing insights from existing data from the clinical monitoring of T cell therapy administration with validation in preclinical and computational models.
4. Production of GMP (Good Manufacturing Practice) guidance and establishment of standard product profiles for autologous and allogeneic engineered T cells to enable production at industry scale and quality, to improve the regulatory process, and to foster dialogue with policymakers.
5. Integrate patient stakeholders into the research and development life cycle of engineered T cell therapy and improve patient experience and interaction with health care practitioners through the joint creation of innovative communication, education, and training tools.
6. Facilitate the expansion of patient access by formulating the outputs of T2EVOLVE in the context of an economic analysis (HTA) to pose recommendations on best paths forward to ensure broad patient access and how engineered T cell therapy could be made more affordable.
Why is T2EVOLVE important to society?
Engineered cell therapy has the potential to offer effective treatment for cancer and other conditions that otherwise would go untreated, leading to increased suffering and death. To realize this potential, T2EVOLVE is aiming at the following key impacts:
• Safer and more effective engineered cell therapies
• Increased access to engineered cell therapy
• Increased health care provider and public awareness of engineered cell therapy
• Accelerated development of new engineered cell therapies
• Increased industrial competitiveness in Europe.
A number of challenges arise because engineered cell therapy is a complex therapeutic approach that works by modifying complex systems within the body. The field needs better models to predict which new therapies will be successful, standards for processes, improved regulations, better awareness of engineered cell therapy and the barriers to access.
To reduce the barriers that are slowing down the development and are limiting access to engineered T cell therapies in Europe, the T2EVOLVE consortium will seek to achieve 6 central objectives:
1. Optimization of pre-clinical (laboratory) models, tools, and pharmacodynamic (PD) markers to better predict toxicity and efficacy of engineered T cell therapies before they enter clinical trials.
2. Definition of gold standard analytical methods pre- and post-T-cell infusion and harmonization of product characterization, release testing, monitoring, long-term (e.g. genomic safety) assessment, to enable inter-product comparability, value attribution, and the development of sustainable reimbursement.
3. Selection of optimal lymphodepletion regimens (pre-treatment chemotherapy) by drawing insights from existing data from the clinical monitoring of T cell therapy administration with validation in preclinical and computational models.
4. Production of GMP (Good Manufacturing Practice) guidance and establishment of standard product profiles for autologous and allogeneic engineered T cells to enable production at industry scale and quality, to improve the regulatory process, and to foster dialogue with policymakers.
5. Integrate patient stakeholders into the research and development life cycle of engineered T cell therapy and improve patient experience and interaction with health care practitioners through the joint creation of innovative communication, education, and training tools.
6. Facilitate the expansion of patient access by formulating the outputs of T2EVOLVE in the context of an economic analysis (HTA) to pose recommendations on best paths forward to ensure broad patient access and how engineered T cell therapy could be made more affordable.
Why is T2EVOLVE important to society?
Engineered cell therapy has the potential to offer effective treatment for cancer and other conditions that otherwise would go untreated, leading to increased suffering and death. To realize this potential, T2EVOLVE is aiming at the following key impacts:
• Safer and more effective engineered cell therapies
• Increased access to engineered cell therapy
• Increased health care provider and public awareness of engineered cell therapy
• Accelerated development of new engineered cell therapies
• Increased industrial competitiveness in Europe.
T2EVOLVE has developed five laboratory models at least five more are in development. The consortium has also produced a set of patient and caregiver reported signs to facilitate the early recognition of CAR-T therapy Toxicities.
A survey on the variability of practices of CAR-T engineered cell analytical assays has resulted in the first pan-European CAR-T immunomonitoring standard that is actively being benchmarked across multiple sites.
A review of lymphodepletion studies revealed that most of the studies are collecting different types of data, making it difficult to compare and combine different studies. As a result, the consortium is planning to work with the EBMT GoCART coalition to conduct a process of determining a minimal set of variables that every study should collect along with their structure.
T2EVOLVE has made recommendations to the European Pharmacopeia and has started to develop GMP protocols for the standardized immune system monitoring and assays for testing the potency of batches of engineered cell therapy. Teams have also started to work with the EMA innovation task force to build awareness and plot the course for modifying regulations to allow for variations of an engineered cell therapy to be more readily approved.
T2EVOLVE conducted a European patient survey on CAR T-cell therapy to gain insights into patients’ experiences, quality of life, and unmet needs.
An online hub of educational material has been created for information on CAR T-cell (engineered cell) therapy with 25 different resources in five different languages.
T2EVOvLE created a strategic framework for working with external stakeholders:
Vision: Every European patient in need has access to safe and effective advanced engineered T-cell therapies. Mission: Build a sustainable translational ecosystem bringing together all stakeholders to accelerate the development of engineered T-cell therapies by addressing all barriers to access.
Purpose: Accelerating development and improving access to engineered T-cell therapy.
Values: Patients first, Trust, Inclusive, Knowledge exchange, Collaboration, Excellence, and Innovation.
Strategic goals:
1. A critical mass of stakeholders working together to improve access.
2. Wide sharing of data and knowledge.
3. Alignment on procedures and processes.
4. Better models and technologies for the development of engineered T-cell therapies.
A survey on the variability of practices of CAR-T engineered cell analytical assays has resulted in the first pan-European CAR-T immunomonitoring standard that is actively being benchmarked across multiple sites.
A review of lymphodepletion studies revealed that most of the studies are collecting different types of data, making it difficult to compare and combine different studies. As a result, the consortium is planning to work with the EBMT GoCART coalition to conduct a process of determining a minimal set of variables that every study should collect along with their structure.
T2EVOLVE has made recommendations to the European Pharmacopeia and has started to develop GMP protocols for the standardized immune system monitoring and assays for testing the potency of batches of engineered cell therapy. Teams have also started to work with the EMA innovation task force to build awareness and plot the course for modifying regulations to allow for variations of an engineered cell therapy to be more readily approved.
T2EVOLVE conducted a European patient survey on CAR T-cell therapy to gain insights into patients’ experiences, quality of life, and unmet needs.
An online hub of educational material has been created for information on CAR T-cell (engineered cell) therapy with 25 different resources in five different languages.
T2EVOvLE created a strategic framework for working with external stakeholders:
Vision: Every European patient in need has access to safe and effective advanced engineered T-cell therapies. Mission: Build a sustainable translational ecosystem bringing together all stakeholders to accelerate the development of engineered T-cell therapies by addressing all barriers to access.
Purpose: Accelerating development and improving access to engineered T-cell therapy.
Values: Patients first, Trust, Inclusive, Knowledge exchange, Collaboration, Excellence, and Innovation.
Strategic goals:
1. A critical mass of stakeholders working together to improve access.
2. Wide sharing of data and knowledge.
3. Alignment on procedures and processes.
4. Better models and technologies for the development of engineered T-cell therapies.
At the outset, T2EVOLVE aimed at advancing the state of the art in six different areas.
1. Deliver pre-clinical models for efficacy and toxicology testing that matters: more than 10 models for toxicology and efficacy testing are in development. Better prediction will mean researchers and companies will be able to avoid substantial investments that end in clinical trial failure.
2. Deliver a breakthrough in harmonized manufacturing and standardized monitoring of engineered cell therapy: T2EVOLVE has been able to leverage the consortium and the associated network to survey a pan-European group of experts to develop an immune monitoring standard.
3. Deliver the premise for the development of allogeneic & off-the-shelf engineered cell therapy products: Specific efforts to build the premise for the development of allogeneic and off-the-shelf therapies will become more of a focus in the latter half of T2EVOLVE. The potential impact of these efforts will be the expansion of access to engineered cell therapy as it will reduce the need to have specialized centers.
4. Involving patient stakeholders in the R&D process: T2EVOLVE has six meetings with patient stakeholders. They have been involved in helping to define a patient experience survey as well as the educational material on the website.
5. Deliver the premise for broad patient access and clinical use of engineered cell therapy:. T2EVOLVE has started to survey stakeholders to identify their perception of the most important barriers to access to engineered cell therapy, T2EVOLVE has begun building an external stakeholder community that will achieve the critical mass to address the challenges T2EVOLVE is working to solve.
1. Deliver pre-clinical models for efficacy and toxicology testing that matters: more than 10 models for toxicology and efficacy testing are in development. Better prediction will mean researchers and companies will be able to avoid substantial investments that end in clinical trial failure.
2. Deliver a breakthrough in harmonized manufacturing and standardized monitoring of engineered cell therapy: T2EVOLVE has been able to leverage the consortium and the associated network to survey a pan-European group of experts to develop an immune monitoring standard.
3. Deliver the premise for the development of allogeneic & off-the-shelf engineered cell therapy products: Specific efforts to build the premise for the development of allogeneic and off-the-shelf therapies will become more of a focus in the latter half of T2EVOLVE. The potential impact of these efforts will be the expansion of access to engineered cell therapy as it will reduce the need to have specialized centers.
4. Involving patient stakeholders in the R&D process: T2EVOLVE has six meetings with patient stakeholders. They have been involved in helping to define a patient experience survey as well as the educational material on the website.
5. Deliver the premise for broad patient access and clinical use of engineered cell therapy:. T2EVOLVE has started to survey stakeholders to identify their perception of the most important barriers to access to engineered cell therapy, T2EVOLVE has begun building an external stakeholder community that will achieve the critical mass to address the challenges T2EVOLVE is working to solve.