Publication
The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.
Journal Paper/Review - Jul 15, 2022
Ferguson Ian D, Patiño-Escobar Bonell, Tuomivaara Sami T, Lin Yu-Hsiu T, Nix Matthew A, Leung Kevin K, Kasap Corynn, Ramos Emilio, Nieves Vasquez Wilson, Talbot Alexis, Hale Martina, Naik Akul, Kishishita Audrey, Choudhry Priya, Lopez-Girona Antonia, Miao Weili, Wong Sandy W, Wolf Jeffrey L, Martin Thomas G, Shah Nina, Vandenberg Scott, Prakash Sonam, Besse Lenka, Driessen Christoph, Posey Avery D, Mullins R Dyche, Eyquem Justin, Wells James A, Wiita Arun P
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Brief description/objective
The myeloma surface proteome (surfaceome) determines tumor interaction with the microenvironment and serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to define the myeloma surfaceome at baseline, in drug resistance, and in response to acute drug treatment. We provide a scoring system for surface antigens and identify CCR10 as a promising target in this disease expressed widely on malignant plasma cells. We engineer proof-of-principle chimeric antigen receptor (CAR) T-cells targeting CCR10 using its natural ligand CCL27. In myeloma models we identify proteins that could serve as markers of resistance to bortezomib and lenalidomide, including CD53, CD10, EVI2B, and CD33. We find that acute lenalidomide treatment increases activity of MUC1-targeting CAR-T cells through antigen upregulation. Finally, we develop a miniaturized surface proteomic protocol for profiling primary plasma cell samples with low inputs. These approaches and datasets may contribute to the biological, therapeutic, and diagnostic understanding of myeloma.