Project description
New CAR-T targets for relapsed NHL
Non-Hodgkin lymphomas (NHL) are aggressive blood cancers characterised by the uncontrolled growth of malignant B lymphocytes, forming tumours throughout the body. Current treatments, including chemotherapy and CAR-T therapy targeting the CD19 protein, show promise but are not universally effective. Approximately 40 % of patients either do not respond well or experience relapse, often due to the loss of CD19 on cancer cells. This highlights a critical need for alternative or additional therapeutic targets. With the support of the Marie Skłodowska-Curie Actions programme, the CARLY project aims to address this issue by developing CAR-T cells targeting a new protein highly expressed in NHL. The project will assess this novel target in a large patient cohort and refine the therapy using advanced preclinical models.
Objective
Non-Hodgkin lymphomas (NHL) are a group of blood cancers characterized by the expansion of malignant B lymphocytes creating tumors throughout the body. The standard of care for patients with aggressive NHL is a combination of chemotherapy and immunotherapy. Even though it is well tolerated, ~40% of the patients respond poorly and eventually relapse. Novel personalized treatment options are now available for such individuals and engage patients’ own T cells genetically manipulated to express a chimeric antigen receptor (CAR) capable to recognize and attack malignant cells. Thus far, CAR-T products recognizing and attacking cells expressing the protein CD19 have been approved by regulatory agencies across the planet. However, long-term follow-up studies show that more than half of these patients eventually succumb to relapse after CAR-T treatment. One of the causes for this is the loss of the CD19 protein on NHL cells. Therefore, finding other proteins beyond CD19 that could be targeted or co-targeted with CAR-T-cells is desired.
Indeed, in the proposed project, I intend to develop and characterize a CAR-T therapy directed against a cell surface protein highly expressed in NHL (preliminary data). Herein, I plan to evaluate the levels of the new target protein in a large cohort of NHL patients using immunohistochemistry and to perform a thorough preclinical assessment of this novel CAR-T-cell approach using cutting-edge preclinical NHL models. To achieve these goals, I will exploit the experience of the hosting institution in generating NHL patient-derived xenografts and in the bench-to-bedside CAR-T development process, as well as the external collaborators who are experts in blood cancer treatment.
This fellowship will significantly expose me to world-class theoretical and hands-on preclinical research in hematooncology and adoptive cell therapy, thus boosting my career as an independent researcher.
Fields of science (EuroSciVoc)
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- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences astronomy planetary sciences planets
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2023-PF-01
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08916 Badalona
Spain
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