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The Road to Personalized Myeloma Medicine: Patient-specific Single-domain Antibodies for Anti-idiotypic Radionuclide Therapy.
Puttemans, Janik; Stijlemans, Benoit; Keyaerts, Marleen; Vander Meeren, Sam; Renmans, Wim; Fostier, Karel; Debie, Pieterjan; Hanssens, Heleen; Rodak, Magdalena; Pruszynski, Marek; De Veirman, Kim; Vanderkerken, Karin; Lahoutte, Tony; Morgenstern, Alfred; Bruchertseifer, Frank; Devoogdt, Nick; D'Huyvetter, Matthias.
Afiliação
  • Puttemans J; Department of Medical Imaging, Laboratory for In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium.
  • Stijlemans B; Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
  • Keyaerts M; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
  • Vander Meeren S; Department of Medical Imaging, Laboratory for In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium.
  • Renmans W; Nuclear Medicine Department, UZ Brussel, Brussels, Belgium.
  • Fostier K; Department of Clinical Biology, Hematology Division, UZ Brussel, Brussels, Belgium.
  • Debie P; Department of Clinical Biology, Hematology Division, UZ Brussel, Brussels, Belgium.
  • Hanssens H; Department of Hematology, OLV Aalst, Aalst, Belgium.
  • Rodak M; Department of Hematology, UZ Brussel, Brussels, Belgium.
  • Pruszynski M; Department of Medical Imaging, Laboratory for In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium.
  • De Veirman K; Department of Medical Imaging, Laboratory for In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium.
  • Vanderkerken K; Institute of Nuclear Chemistry and Technology, Warsaw, Poland.
  • Lahoutte T; Institute of Nuclear Chemistry and Technology, Warsaw, Poland.
  • Morgenstern A; Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
  • Bruchertseifer F; Department of Hematology and Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
  • Devoogdt N; Department of Hematology and Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
  • D'Huyvetter M; Department of Medical Imaging, Laboratory for In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium.
Mol Cancer Ther ; 21(1): 159-169, 2022 01.
Article em En | MEDLINE | ID: mdl-34667109
To this day, multiple myeloma remains an incurable cancer. For many patients, recurrence is unavoidably a result of lacking treatment options in the minimal residual disease stage. This is due to residual and treatment-resistant myeloma cells that can cause disease relapse. However, patient-specific membrane-expressed paraproteins could hold the key to target these residual cells responsible for disease recurrence. Here, we describe the therapeutic potential of radiolabeled, anti-idiotypic camelid single-domain antibody fragments (sdAbs) as tumor-restrictive vehicles against a membrane-bound paraprotein in the syngeneic mouse 5T33 myeloma model and analogously assess the feasibility of sdAb-based personalized medicine for patients with multiple myeloma. Llamas were immunized using extracts containing paraprotein from either murine or human sera, and selective sdAbs were retrieved using competitive phage display selections of immune libraries. An anti-5T33 idiotype sdAb was selected for targeted radionuclide therapy with the ß--particle emitter 177Lu and the α-particle emitter 225Ac. sdAb-based radionuclide therapy in syngeneic mice with a low 5T33 myeloma lesion load significantly delayed tumor progression. In five of seven patients with newly diagnosed myeloma, membrane expression of the paraprotein was confirmed. Starting from serum-isolated paraprotein, for two of three selected patients anti-idiotype sdAbs were successfully generated.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Radioisótopos / Medicina de Precisão / Anticorpos de Domínio Único / Mieloma Múltiplo Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Radioisótopos / Medicina de Precisão / Anticorpos de Domínio Único / Mieloma Múltiplo Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article