Datasets

Title	Developing High-Affinity Decoy Receptor Optimized for Multiple Myeloma and Diffuse Large B Cell Lymphoma Treatment [Ribo-seq]
Organism
Number of Samples	12
Release Date	2022/06/13 00:00
Sequencing Types
Protocol Details

Title
Authors	Miao YR, Thakkar K, Cenik C, Jiang D, Mizuno K, Jia C, Li CG, Zhao H, Diep A, Xu Y, Zhang XE, Yang TTC, Liedtke M, Abidi P, Leung WS, Koong AC, Giaccia AJ
Journal	The Journal of experimental medicine
Publication Date	2022 Sep 5
Abstract	Disease relapse and treatment-induced immunotoxicity pose significant clinical challenges for patients with hematological cancers. Here, we reveal distinctive requirements for neutralizing TNF receptor ligands APRIL and BAFF and their receptor activity in MM and DLBCL, impacting protein translation and production in MM cells and modulating the translation efficiency of the ATM interactor (ATMIN/ACSIZ). Therapeutically, we investigated the use of BCMA decoy receptor (sBCMA-Fc) as an inhibitor of APRIL and BAFF. While wild-type sBCMA-Fc effectively blocked APRIL signaling in MM, it lacked activity in DLBCL due to its weak BAFF binding. To expand the therapeutic utility of sBCMA-Fc, we engineered an affinity-enhanced mutant sBCMA-Fc fusion molecule (sBCMA-Fc V3) 4- and 500-fold stronger in binding to APRIL and BAFF, respectively. The mutant sBCMA-Fc V3 clone significantly enhanced antitumor activity against both MM and DLBCL. Importantly, we also demonstrated an adequate toxicity profile and on-target mechanism of action in nonhuman primate studies. © 2022 Miao et al.
PMC	PMC9428257
PMID	35881112
DOI

Miao et al. 2022 (PRJNA848829)