Data from The Road to Personalized Myeloma Medicine: Patient-specific Single-domain Antibodies for Anti-idiotypic Radionuclide Therapy Article Swipe

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Janik Puttemans , Benoı̂t Stijlemans , Marleen Keyaerts , Sam Vander Meeren , Wim Renmans , Karel Fostier , Pieterjan Debie , Heleen Hanssens , Magdalena Rodak , Marek Pruszyński , Kim De Veirman , Karin Vanderkerken , Tony Lahoutte , Aliyah Morgenstern , Frank Bruchertseifer , Nick Devoogdt , Matthias D’Huyvetter ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1158/1535-7163.c.6493080

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 β⁻-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.

Related Topics

Multiple Myeloma

Single-Domain Antibody

Concepts

Idiotype Multiple myeloma Single-domain antibody Antibody Medicine Internalization Paraproteins Cancer research Immunoglobulin light chain Immunology Molecular biology Internal medicine Biology Monoclonal antibody Monoclonal Receptor

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/1535-7163.c.6493080
OA Status: gold
Related Works: 10
OpenAlex ID: https://openalex.org/W4361268576

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DOI: https://doi.org/10.1158/1535-7163.c.6493080

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Title: Data from The Road to Personalized Myeloma Medicine: Patient-specific Single-domain Antibodies for Anti-idiotypic Radionuclide Therapy

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Type: preprint

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Language: en

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Publication year: 2023

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Publication date: 2023-03-30

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Authors: Janik Puttemans, Benoı̂t Stijlemans, Marleen Keyaerts, Sam Vander Meeren, Wim Renmans, Karel Fostier, Pieterjan Debie, Heleen Hanssens, Magdalena Rodak, Marek Pruszyński, Kim De Veirman, Karin Vanderkerken, Tony Lahoutte, Aliyah Morgenstern, Frank Bruchertseifer, Nick Devoogdt, Matthias D’Huyvetter

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Landing page: https://doi.org/10.1158/1535-7163.c.6493080

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Concepts: Idiotype, Multiple myeloma, Single-domain antibody, Antibody, Medicine, Internalization, Paraproteins, Cancer research, Immunoglobulin light chain, Immunology, Molecular biology, Internal medicine, Biology, Monoclonal antibody, Monoclonal, Receptor

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abstract_inverted_index.targeted	133
abstract_inverted_index.vehicles	74
abstract_inverted_index.anti-5T33	127
abstract_inverted_index.diagnosed	170
abstract_inverted_index.fragments	70
abstract_inverted_index.immunized	102
abstract_inverted_index.incurable	7
abstract_inverted_index.patients,	11
abstract_inverted_index.potential	63
abstract_inverted_index.retrieved	117
abstract_inverted_index.selective	114
abstract_inverted_index.syngeneic	81, 150
abstract_inverted_index.treatment	19
abstract_inverted_index.confirmed.	178
abstract_inverted_index.containing	105
abstract_inverted_index.expression	173
abstract_inverted_index.libraries.	125
abstract_inverted_index.recurrence	12
abstract_inverted_index.sdAb-based	92, 146
abstract_inverted_index.selections	122
abstract_inverted_index.analogously	87
abstract_inverted_index.competitive	119
abstract_inverted_index.feasibility	90
abstract_inverted_index.paraprotein	78, 106, 176
abstract_inverted_index.recurrence.	57
abstract_inverted_index.responsible	54
abstract_inverted_index.therapeutic	62
abstract_inverted_index.unavoidably	14
abstract_inverted_index.α-particle	143
abstract_inverted_index.paraprotein,	182
abstract_inverted_index.paraproteins	44
abstract_inverted_index.personalized	93
abstract_inverted_index.progression.	162
abstract_inverted_index.radionuclide	134, 147
abstract_inverted_index.successfully	192
abstract_inverted_index.anti-idiotype	189
abstract_inverted_index.radiolabeled,	65
abstract_inverted_index.significantly	159
abstract_inverted_index.single-domain	68
abstract_inverted_index.anti-idiotypic	66
abstract_inverted_index.membrane-bound	77
abstract_inverted_index.serum-isolated	181
abstract_inverted_index.patient-specific	42
abstract_inverted_index.tumor-restrictive	73
abstract_inverted_index.membrane-expressed	43
abstract_inverted_index.treatment-resistant	33
abstract_inverted_index.<sup>177</sup>Lu	140
abstract_inverted_index.<sup>225</sup>Ac.	145
abstract_inverted_index.<div>Abstract<p>To	0
abstract_inverted_index.generated.</p></div>	193
abstract_inverted_index.β<sup>−</sup>-particle	138
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	17
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