Blood malignancy such as chronic myeloid leukemia (CML) and lymphomas are pathologies dealing with a high relapse rate. Allogeneic hematopoietic stem cell transplantation (Allo-HCT) and Donor lymphocyte injections (DLI) are among potential strategies to treat or prevent relapse, however, response rate generally remains low. Treg cells play a key role in the fine tuning of the immune responses in alloHCT. Cell therapy using Treg infusions to prevent graft-versus-host disease (GVHD) showed very promising results in the clinic. Conversely, ex vivo Treg depletion from DLI has been shown to enhance the graft-versus-leukemia (GVL) effect in patients who relapsed after alloHCT without previously developing GVHD. Using an anti-TNFR2 mAb, the team provided proof of concept that an anti-TNFR2 treatment can mediate a potent GVL/GVT effect in different experimental models of hematological malignancy relapse after alloSCT through inhibition of Treg population. These results pave the way toward a novel immune checkpoint therapy to modulate alloreactivity after allo-HCT through the TNF/TNFR2 signaling pathway and, more widely, open new perspectives to amplify antitumor responses in solid cancers by directly targeting Tregs and tumor cells through their TNFR2 expression.
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Keywords : Graft versus Leukemia (GvL), TNFR2 Monoclonal antibody, Donor lymphocytes infusion (DLI), Treg lymphocytes, Alloreactivity