Objective
We propose to make human T cells that bear chimeric receptors specific for CD33, a leukemia-associated antigen, and demonstrate that they are cytotoxic to human myeloid malignancies expressing this target antigen. However, the lack of stimulation through t he native T-cell immune receptor and the paucity of costimulatory molecules on the leukemia cells limit the survival, growth and functional activity of these chimeric effector cells once they are re-injected in vivo in patients. We plan to overcome this limitation by incorporating the CD33 chimeric receptor into cytotoxic T cells specific for EBV antigens (chimeric EBV-CTLs).
EBV antigens are persistently expressed by B cells in vivo, together with high levels of costimulatory molecules. Hence, they may provide the native receptor and costimulatory signals needed to sustain and expand the modified effector cells for their subsequent interaction with leukemic cells through their chimeric CD33 receptor. We will test our hypothesis in three aims. In Aim 1, we will compare the in vitro cytotoxic activities of chimeric EBV-CTLs with those of unselected chimeric T cells from EBV-seropositive patients with advanced CD33+ myeloid malignancies against established myeloid leukemia cell lines or primary myeloid blasts. In Aim 2, we will enhance T-cell activation by introducing costimulatory elements into the signalling domain of chimeric receptors expressed on the T-cell surface. In Aim 3, we will evaluate the antileukemic activity of chimeric T cells against a human CD33+ AML in vivo in NOD-SCID mice. If effective, we will seek approval to initiate a phase I/II clinical trial of chimeric CTLs in EBV-seropositive patients with relapsed or high-risk CD33+ leukemia.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology leukemia
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2004-MOBILITY-12
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Funding Scheme
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.
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.
IRG - Marie Curie actions-International re-integration grants
Coordinator
LYON
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.