RT Journal Article
SR Electronic
T1 Defining the cell surface proteomic landscape of multiple myeloma reveals immunotherapeutic strategies and biomarkers of drug resistance
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.17.427038
DO 10.1101/2021.01.17.427038
A1 Ian D. Ferguson
A1 Bonell Patiño Escobar
A1 Sami T. Tuomivaara
A1 Yu-Hsiu T. Lin
A1 Matthew A. Nix
A1 Kevin K. Leung
A1 Martina Hale
A1 Priya Choudhry
A1 Antonia Lopez-Girona
A1 Emilio Ramos
A1 Sandy W. Wong
A1 Jeffrey L. Wolf
A1 Thomas G. Martin III
A1 Nina Shah
A1 Scott Vandenberg
A1 Sonam Prakash
A1 Lenka Besse
A1 Christoph Driessen
A1 James A. Wells
A1 Arun P. Wiita
YR 2021
UL http://biorxiv.org/content/early/2021/01/19/2021.01.17.427038.abstract
AB The myeloma cell surface proteome (“surfaceome”) not only determines tumor interaction with the microenvironment but serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to first define surface markers most-enriched on myeloma when compared to B-cell malignancy models, revealing unexpected biological signatures unique to malignant plasma cells. We next integrate our proteomic dataset with existing transcriptome databases, nominating CCR10 and TXNDC11 as possible monotherapeutic targets and CD48 as a promising co-target for increasing avidity of BCMA-directed cellular therapies. We further identify potential biomarkers of resistance to both proteasome inhibitors and lenalidomide including changes in CD53, EVI2B, CD10, and CD33. Comparison of short-term treatment with chronic resistance delineates large differences in surface proteome profile under each type of drug exposure. Finally, we develop a miniaturized version of the surface proteomics protocol and present the first surface proteomic profile of a primary myeloma patient plasma cell sample. Our dataset provides a unique resource to advance the biological, therapeutic, and diagnostic understanding of myeloma.Competing Interest StatementA.P.W. is a member of the Scientific Advisory Board and holds equity stakes in Indapta Therapeutics and Protocol Intelligence, LLC. J.A.W. is on the Scientific Advisory Board and holds equity stakes in the following companies with oncology interests: Soteria Biotherapeutics, Jnana Therapeutics, Inception Therapeutics, and Inzen Therapeutics, and holds a sponsored research agreement with Bristol Myers Squibb. S.W.W. has received research funding from Janssen, GlaxoSmithKline, Bristol Myers Squibb, Genentech, and Fortis, and served as a consultant to Amgen. T.G.M. has received research funding from Sanofi, Janssen, and Amgen and has served as a consultant to GlaxoSmithKline. A. L.-G. is an employee and shareholder of Celgene/Bristol Myers Squibb. P.C. is currently an employee and shareholder of Roche/Genentech but was solely employed by UCSF during her participation on this project. The other authors declare no relevant conflicts of interest.