IT4B-ALL
Financiado
Therapeutic immunotherapy targeting NG2 and CD22 antigens for MLL rearranged and...
Therapeutic immunotherapy targeting NG2 and CD22 antigens for MLL rearranged and MLL germline B cell Acute Lymphoblastic Leukemia
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 re...
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 CD34+CD22+CD19- 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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Duración del proyecto: 21 meses
Fecha Inicio: 2018-09-17
Fecha Fin: 2020-06-30
Fecha Fin: 2020-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-06-30
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2018-PoC:
ERC Proof of Concept Grant
Cerrada
hace 6 años
Presupuesto
El presupuesto total del proyecto asciende a
150K€
Líder del proyecto
FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEM...
Actividades de investigación asociacion
Perfil tecnológico
TRL
4-5
50K
Perfil tecnológico
TRL
4-5
50K