The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance

Ian D. Ferguson, Bonell Patiño-Escobar, Sami T. Tuomivaara, Yu-Hsiu T. Lin, Matthew A. Nix, Kevin K. Leung, Corynn Kasap, Emilio Ramos, Wilson Nieves Vasquez, Alexis Talbot, Martina Hale, Akul Naik, Audrey Kishishita, Priya Choudhry, Antonia Lopez-Girona, Weili Miao, Sandy W. Wong, Jeffrey L. Wolf, Thomas G. Martin, Nina Shah, Scott Vandenberg, Sonam Prakash, Lenka Besse, Christoph Driessen, Avery D. Posey, R. Dyche Mullins, Justin Eyquem, James A. Wells and Arun P. Wiita ()
Additional contact information
Ian D. Ferguson: University of California
Bonell Patiño-Escobar: University of California
Sami T. Tuomivaara: University of California
Yu-Hsiu T. Lin: University of California
Matthew A. Nix: University of California
Kevin K. Leung: University of California
Corynn Kasap: University of California
Emilio Ramos: University of California
Wilson Nieves Vasquez: University of California
Alexis Talbot: University of California
Martina Hale: University of California
Akul Naik: University of California
Audrey Kishishita: University of California
Priya Choudhry: University of California
Antonia Lopez-Girona: Bristol Myers Squibb/Celgene
Weili Miao: Stanford University School of Medicine
Sandy W. Wong: University of California
Jeffrey L. Wolf: University of California
Thomas G. Martin: University of California
Nina Shah: University of California
Scott Vandenberg: University of California
Sonam Prakash: University of California
Lenka Besse: Kantonsspital St. Gallen
Christoph Driessen: Kantonsspital St. Gallen
Avery D. Posey: University of Pennsylvania School of Medicine
R. Dyche Mullins: University of California
Justin Eyquem: University of California
James A. Wells: University of California
Arun P. Wiita: University of California

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31810-6

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