Decoy-based, targeted inhibition of STAT3: A new step forward for B cell lymphoma immunotherapy

Abstract

Increasing evidence has linked the aggressiveness of non-Hodgkin’s lymphoma, in particular activated B cell-like type diffuse large B cell lymphomas (ABC-DLBCL), to signaling by toll-like receptor 9 (TLR9)/ MyD88 and STAT3. In this issue of Molecular Therapy, Zhao et al.1 describe a dual function molecule comprising a clinically-relevant TLR9 agonist (CpG7909) fused to a STAT3 inhibitor in the form of a high-affinity decoy oligodeoxynucleotide (dODN). CpG-STAT3dODN blocked STAT3 DNA binding and activity, thus reducing expression of downstream target genes, such as MYC and BCL2L1, in human and mouse lymphoma cells. These effects led to the generation of lymphoma cell-specific CD8/ CD4-dependent T cell immunity that could protect mice from tumor rechallenge.