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InTheMLLrBALL SIGNED

Innovative Therapeutic Strategies for Mixed Lineage Leukemia-rearranged B-cell Acute Lymphoblastic Leukemia

Total Cost €

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EC-Contrib. €

0

Partnership

0

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 InTheMLLrBALL project word cloud

Explore the words cloud of the InTheMLLrBALL project. It provides you a very rough idea of what is the project "InTheMLLrBALL" about.

combination    contribution    cell    fundamental    children    lineage    commonest    bispecific    microenvironment    acute    mediated    l1    refractory    mixed    immunotherapy    chemotherapy    mllr    engineered    indirect    lymphoblastic    shown    vitro    scientific    strategy    immune    cars    mechanism    car    pd1l    occurs    interplay    vivo    leukemia    clinically    antigen    benefited    persistence    training    dismal    pd    molecule    mainly    efficacy    clinical    surface    receptors    transfer    near    stroma    cells    alls    cd19    blockade    host    blasts    adoptive    stromal    efficiency    prognosis    mesenchymal    artificial    offset    modify    escape    independent    express    cutting    domains    binding    cancer    single    complementary    mllrb    chimeric    containing    pd1    d1    trials    disease    rearrangements    with    therapy    ag    ng2    impressive    tandem    remission    edge    reduce    tumor    responded    relapse    pressure    leadership    plan    position    patients   

Project "InTheMLLrBALL" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS 

Organization address
address: CARRER MUNTANER 383 3/2
city: BARCELONA
postcode: 8021
website: www.carrerasresearch.org

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Spain [ES]
 Total cost 158˙121 €
 EC max contribution 158˙121 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-04-01   to  2020-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS ES (BARCELONA) coordinator 158˙121.00

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 Project objective

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest cancer in children and B-ALL with mixed-lineage leukemia rearrangements (MLLr) has a particularly dismal prognosis compared with other B-ALLs. Many MLLrB-ALL patients are refractory to chemotherapy and eventually relapse. Thus, MLLrB-ALL remains clinically challenging. Adoptive transfer of T cells engineered to express artificial chimeric antigen (Ag) receptors (CARs) targeting tumor cell surface-specific Ag is an exciting new approach for cancer immunotherapy. Clinical trials in patients with advanced B-ALL treated with CAR-T cells against CD19 have shown impressive disease remission; however relapse still occurs with loss of CD19. Importantly, the B-ALL patients who have not responded to CD19 CAR-T cells were mainly those carrying MLLr. A strategy to offset tumor Ag-loss relapse is to modify T cells with one CAR molecule containing two different binding domains in tandem (bispecific CAR). By using both in vitro and in vivo approaches, I plan to improve CD19 CAR-T cell therapy for MLLrB-ALL by i)developing a novel bispecific CD19/NG2 CAR, which we expect will reduce single-Ag immune pressure, and ii)through the combination of CD19 CAR-T cell therapy with P-D1/PD-L1 blockade. How to achieve a long-term persistence of CAR-T cells in the host still remains a major challenge in adoptive T cell immunotherapy, and therefore understanding the interplay between T cells, MLLrB-ALL blasts and mesenchymal stromal cells/stroma is fundamental to improve the efficiency of this immunotherapy. We will thus address in vitro and in vivo the contribution of the leukemia microenvironment to CAR-T cell efficacy, as a potential tumor microenvironment (PD1/PD1L)-mediated indirect mechanism of immune escape to CAR T-cells. This cutting-edge proposal will increase my scientific potential and I will be benefited with the complementary/leadership training activities already planned to reach in a near future an independent position.

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