Project Details
Projekt
Combination of a CD19 antibody of IgA isotype and CD47 inhibition for the treatment of BCP-ALL
Subject Area
Hematology, Oncology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 444949889
Immune therapy has become an important part of ALL treatment, mainly because CD19-directed immunotherapies opened new avenues. Myeloid effector cells such as macrophages play important roles in immune surveillance and may also mediate anti-leukemic effects of monoclonal antibodies. We have shown that an optimized CD19 IgG1 antibody can activate antibody-dependent cellular phagocytosis and cause clinical cure in murine models of minimal residual disease in B cell precursor ALL. Myeloid effector cell activation can be improved by using IgA instead of IgG antibodies for immunotherapy. Also, inhibition of the myeloid immune checkpoint CD47/SIRP-alpha can make immunotherapies very efficient by inhibiting an important “don’t-eat-me” signal. In this project, we hypothesize that the combination of a CD19-IgA antibody with blockade of CD47 will result in improved recruitment of myeloid effector cells and therefore enhance the preclinical efficacy of CD19-directed immunotherapies in vitro and in vivo. The results of the experiments proposed will constitute the basis for the translation of clinical protocols combining anti-CD19 therapy with CD47 blockade into early phase clinical trials in adult and pediatric ALL.
DFG Programme
Clinical Research Units
Subproject of
KFO 5010:
CATCH ALL Towards a Cure for Adults and Children with Acute Lymphoblastic Leukemia (ALL)
International Connection
Netherlands
Cooperation Partner
Professorin Dr. Jeanette Leusen
