OSR: Core activities within CARAT
OSR is the leading private scientific research Institute in Italy, recognized by the Italian Ministry of Health as a Research Hospital (IRCCS). It comprises both clinical and research activities, conducted within a highly specialized and qualified Hospital, and clinical as well as translational research. The premises also host the Vita-Salute San Raffaele University (USR), which comprises the faculties of medicine, psychology and philosophy and provides specialized post-graduate courses, residency programs in various medical specialties, and International PhD programs. OSR performs cutting-edge science and aims at advancing the knowledge about human diseases and developing novel therapies through translational research. In particular OSR excellence areas are: Oncology; Neuroscience; Metabolic and Cardiovascular Sciences; Regenerative Medicine, Stem Cells and Gene Therapy; Immunology, Transplantation and Infectious Diseases; Genetics and Cell Biology; Genomics, Bioinformatics and Imaging technologies.
Major determinants for successful CAR-T cell therapy in cancer patients include rapid expansion and long-term persistence of infused cells, as well as the execution of potent effector functions. As Work Package leader of WP1, OSR is responsible for the design and generation of biologically improved CAR T-cells. They are devoted to the identification of key factors to manufacture biologically-enhanced CAR-T cells (activation protocol, starting cell subset, co-stimulation). Especially, OSR is exploiting its unique experience with innovative efficacy/toxicity in vivo models to identify cell products with improved therapeutic indexes. Additionally, OSR will participate to the validation of the conditions for GMP manufacturing of improved CAR-T cells, with the ultimate goal of clinical translation.
Question & Answers from the OSR Team
Innovative immunotherapy strategies like CAR-T cell therapy have the potential to revolutionize the way of treating cancer patients, offering them a real opportunity to be cured. Due to the complexity of these approaches, deepening the knowledge of CAR-T cell biology and developing innovative preclinical models is crucial to increase responses, reduce toxicities and widen the applicability of these therapies to other cancers besides B-cell malignancies. This is the main focus of my research activity.
What is your research focus at OSR?
I’m in charge of the CAR-T cell therapy programme for cancer treatment at OSR and, besides CARAT, I’m involved in two other EU funded H2020 Consortia (EURE-CART and CARAMBA) aimed at promoting the bench-to-bedside translation of CAR-T cell therapies in Europe. Currently, our research activities include the improvement of CAR-T cell fitness, the development of combined approaches to increase the potency of CAR-T cell therapy against solid malignancies and the study of CAR-T cell biology in innovative xenograft mouse models. During my research experience I developed a new CAR-based strategy targeting CD44v6 to tackle acute myeloid leukemia and multiple myeloma that has recently received approval by AIFA for testing in a first in man clinical trial in patients.
What are OSR’s specific challenges in CARAT’s final year?
Presently, OSR is deepening the study on the efficacy/toxicity profile of biologically-enhanced CAR-T cell products in complex preclinical in vivo models. Moreover, OSR is verifying if results obtained with T cells derived from healthy donors can be translated to T cells derived from cancer patients.
What is your personal motivation?
Innovative immunotherapy strategies like CAR-T cell therapy have the potential to revolutionize the way of treating cancer patients, offering them a real opportunity to be cured. Due to the complexity of these approaches, deepening the knowledge of CAR-T cell biology and developing innovative preclinical models is crucial to increase responses, reduce toxicities and widen the applicability of these therapies to other cancers besides B-cell malignancies. This is the main focus of my research activity.
It is really inspiring to be able to observe the development of a possible cure for so many patients starting from the bench to the clinical testing. It really gives perspective to all our hard work and the compromises, such as animal experimentation, that have to be accepted in order to reach this goal.
What expertise are you bringing to the project?
I am responsible for all in vivo experiments at OSR in the CARAT project. In particular, I actively helped establishing the innovative animal models at disposal of the group, and I am always available to offer my experience in animal handling for all the different scientific questions arising in the project.
Why is this field of research so exciting?
It is really inspiring to be able to observe the development of a possible cure for so many patients starting from the bench to the clinical testing. It really gives perspective to all our hard work and the compromises, such as animal experimentation, that have to be accepted in order to reach this goal.
How do you see the field of CAR therapy evolving in the future?
I completely support the idea that this therapy has the potential to be an answer for all the people who nowadays do not have any additional way to fight cancer.
It is really fascinating to be part of such an international consortium. I particularly enjoy the exchange of ideas coming from people all working in the same field of research from different perspectives.
What are your key activities in the project?
I contribute to all experiments needed to conclude the OSR part of the CARAT project. I follow all the different parts of the experiments, from the in vitro analysis and validation of the CAR-T cells to infusion in vivo to assess their efficacy and safety profile.
In your opinion, what is special about CARAT? What motivates you?
It is really fascinating to be part of such an international consortium. I particularly enjoy the exchange of ideas coming from people all working in the same field of research from different perspectives.
Where do you see the future challenges in the field of cell and gene therapy?
It will probably be crucial for this field to keep up the continuous innovation of the cell product needed to facilitate patient access to this particular medical therapy. It would be interesting also to develop a strategy that will enable an “off-the-shelf” approach for T cell therapy.
We have recently had the pleasure to host a CARAT researcher from partner PEI for a collaborative experiment. It was really inspiring to see how our different expertise combined to find a solution for a scientific question that would not have been answered otherwise.
What are your specific tasks in OSR’s CARAT team?
I manage all the in vitro activities concerning production and quality assessment of CARAT-compliant, biologically active CAR-T cells starting from healthy and patient-derived T cells. In particular, I am collaborating in experiments aimed at comparing the efficacy of CAR-T cell products generated from different memory subpopulations. Moreover, I handle standardized CAR-T cell production for in vivo efficacy and safety studies.
What are “your” major achievements?
I have actively contributed to the generation of an optimized research-grade protocol used in all CARAT experiments.
What is most exciting about being part of an international collaborative research programme like CARAT?
We have recently had the pleasure to host a CARAT researcher from partner PEI for a collaborative experiment. It was really inspiring to see how our different expertise combined to find a solution for a scientific question that would not have been answered otherwise.
The integration of so many different points of view really gives perspective to our academic work, both in terms of CAR-T cell biology understanding and the hope of therapy development in the next few years.
What is your role in the OSR team?
I give support to the overall management of the project. In addition, I oversee the scientific writing of reports and publications in high-impact journals and assist in maintaining the communication within the consortium. Moreover, I interact with different OSR offices (legal, administrative, financial) in order to streamline all the different parts of the project.
Why is working in an international collaborative project like CARAT so interesting for you?
It is so interesting because it gives me the opportunity to gain insight into different areas that I could not encounter otherwise, such as foreign laboratories and companies like Miltenyi.
In your opinion, what are the long-term benefits of the CARAT programme?
The integration of so many different points of view really gives perspective to our academic work, both in terms of CAR-T cell biology understanding and the hope of therapy development in the next few years.
The inspiring part of this consortium is the possibility of working on a product that will be translated to the clinics in the near future. I firmly believe that our effort to reduce production process and cost will really enable CAR-T therapy to become a more accessible therapeutic option for all patients.
What is your role in the CARAT team at OSR?
My role as a post-doc in the OSR team is to supervise the conclusion of the project. In particular I contribute to planning the experiments and analyzing the results, so as to better unravel their biological relevance.
What makes working the CARAT consortium so special for you?
The inspiring part of this consortium is the possibility of working on a product that will be translated to the clinics in the near future. I firmly believe that our effort to reduce production process and cost will really enable CAR-T therapy to become a more accessible therapeutic option for all patients.
Where do you see your tasks in the CAR therapy for the future?
I reckon that there is still room for improvement in ameliorating the fitness of the CAR-T cell product, to enhance their efficacy and persistence within the patient. Moreover, I will actively contribute to translate this therapy form haematological to solid malignancies, which represents the great challenge of the field.