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The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.
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.
Afiliação
  • Ferguson ID; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Patiño-Escobar B; Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Tuomivaara ST; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Lin YT; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Nix MA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Leung KK; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Kasap C; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Ramos E; Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, CA, USA.
  • Nieves Vasquez W; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Talbot A; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.
  • Hale M; Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, CA, USA.
  • Naik A; INSERM U976, Institut de Recherche Saint Louis, Université de Paris, Paris, France.
  • Kishishita A; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Choudhry P; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Lopez-Girona A; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Miao W; Program in Chemistry and Chemical Biology, University of California, San Francisco, CA, USA.
  • Wong SW; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Wolf JL; Bristol Myers Squibb/Celgene, San Diego, CA, USA.
  • Martin TG; Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
  • Shah N; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Vandenberg S; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Prakash S; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Besse L; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Driessen C; Department of Pathology, University of California, San Francisco, CA, USA.
  • Posey AD; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Mullins RD; Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Eyquem J; Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Wells JA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
  • Wiita AP; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Nat Commun ; 13(1): 4121, 2022 07 15.
Article em En | MEDLINE | ID: mdl-35840578
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mieloma Múltiplo Tipo de estudo: Guideline / Prognostic_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mieloma Múltiplo Tipo de estudo: Guideline / Prognostic_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos