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IT4B-ALL SIGNED

Therapeutic immunotherapy targeting NG2 and CD22 antigens for MLL-rearranged and MLL-germline B-cell Acute Lymphoblastic Leukemia

Total Cost €

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EC-Contrib. €

0

Partnership

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 IT4B-ALL project word cloud

Explore the words cloud of the IT4B-ALL project. It provides you a very rough idea of what is the project "IT4B-ALL" about.

mll    switch    first    surface    monoclonal    cancer    adult    protected    resistance    commonest    expression    all    2014    marker    immunotherapeutic    ineffectual    antibody    antigen    launch    trial    pressure    escaping    ing    therapies    subgroups    cd19    strategy    cd19neg    pan    preclinical    erc    gmp    overarching    ng2    massive    options    consolidate    infant    antigens    emerged    anti    found    car    worse    circumvent    valid    solely    representing    respectively    refractory    epi173825514    relapse    rapid    glucocorticoid    developmentally    impressive    frequently    losing    immunotherapies    retained    rearrangements    cd34    academic    mllr    progenitors    lineage    proportion    phasei    cd22    prognosis    cns    efficacy    malignant    opposite    combined    dismal    expressed    preleukemic    demonstration    clinical    childhood    therapeutic    relatively    cd34cd22cd19    car19    germline    shown    patent    myeloid    cog    infiltration    therapy    proof    cells    aggressiveness    relapses    cell    earlier   

Project "IT4B-ALL" 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 150˙000 €
 EC max contribution 150˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-PoC
 Funding Scheme ERC-POC
 Starting year 2019
 Duration (year-month-day) from 2019-01-01   to  2020-06-30

 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 150˙000.00

Map

 Project objective

B-ALL is the commonest cancer of childhood. There remain childhood B-ALL subgroups with dismal prognosis such as infant B-ALL and B-ALL carrying MLL rearrangements (MLLr). In addition, the prognosis of adult B-ALL is worse, and refractory/relapse (R/R) B-ALL remains dismal. CD19-targeted immunotherapies have emerged as promising therapeutic approaches for R/R B-ALL. CD19 CAR T-cells have shown impressive efficacy in R/R B-ALL. However, relatively rapid relapses are frequently observed, a proportion of them losing CD19 expression upon CAR19 T-cell therapy due to massive antigen pressure over CD19, resulting in a myeloid lineage switch in MLLr B-ALL, or the selection of CD19-/CD34 preleukemic progenitors. Further CD19-targeted therapy is thus ineffectual for CD19neg R/R B-ALL. Our overarching goal is to provide novel therapeutic options for (R/R) B-ALL.Targeting surface antigens whose expression, opposite to CD19, are commonly retained at relapse is a valid strategy to circumvent the loss of CD19 found in (R/R) B-ALL after CD19-targeted therapies. Recent work funded by my ERC-2014-CoG has identified NG2 and CD22 as key antigens to be targeted in (R/R) B-ALL. First, both antigens are retained in CD19neg R/R B-ALL. Second, NG2 is solely expressed in MLLr B-ALL, and is associated with CNS infiltration, aggressiveness and glucocorticoid resistance. Third, CD22 is a pan-B marker expressed developmentally earlier than CD19, and CD34CD22CD19- cells may represent pre-malignant progenitors escaping the CD19-targeted pressure. These results have just been protected by a European Patent (EPI173825514), and are the proof-of-principle demonstration of NG2 & CD22 representing promising immunotherapeutic targets, when combined with CD19 for both MLLr & MLL-germline B-ALL, respectively. Here we propose to consolidate preclinical work and GMP production of anti-NG2 monoclonal antibody and NG2/CD19 and CD22/CD19 CAR T-cells to launch a PhaseI academic clinical trial for R/R B-ALL

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