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Development and characterization of a novel CAR T-cell therapy for NHL

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.

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Programme(s)

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Topic(s)

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Funding Scheme

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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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Coordinator

FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 226 441,20
Address
CARRETERA DE CAN RUTI CAMI DE LES ESCOLES S/N
08916 Badalona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
Total cost

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Partners (1)

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