B-ALL is the most common cancer during childhood. There are still 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 than that in children, and refractory/relapse (R/R) B-ALL remains dismal. CD19-targeted immunotherapies including CD19-redirected CAR T-cells have emerged as very promising therapeutic approaches for R/R B-ALL. However, relatively rapid relapses are frequently observed after CD19 CAR T-cell treatment, and a proportion of them involve antigen loss due to massive antigen pressure over CD19 or the selection of CD19- preleukemic progenitors. New targeted therapies are therefore in high demand for B-ALL patients relapsing as CD19neg after CD19 CAR T-cell therapy.
The overarching goal of this project 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.
In this ERC-PoC project we have explored the potential of targeting either NG2 or CD22 in B-ALL. This project has produced several peer-review scientific publication in leading journals of hematology and has allowed to fill in two patents to strengthen our IP position. The CD22 patent has been licensed to a Capital Venture-invested spin-off company (One Chain Immunotherapeutics) for clinical development and commercialization of such immunotherapies.
