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Specific Targeting of Lymphoma Cells Using Semisynthetic Anti-Idiotype Shark Antibodies

Macarrón Palacios, Arturo ; Grzeschik, Julius ; Deweid, Lukas ; Krah, Simon ; Zielonka, Stefan ; Rösner, Thies ; Peipp, Matthias ; Valerius, Thomas ; Kolmar, Harald (2024)
Specific Targeting of Lymphoma Cells Using Semisynthetic Anti-Idiotype Shark Antibodies.
In: Frontiers in Immunology, 2020, 11
doi: 10.26083/tuprints-00017467
Article, Secondary publication, Publisher's Version

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Item Type: Article
Type of entry: Secondary publication
Title: Specific Targeting of Lymphoma Cells Using Semisynthetic Anti-Idiotype Shark Antibodies
Language: English
Date: 12 March 2024
Place of Publication: Darmstadt
Year of primary publication: 26 November 2020
Place of primary publication: Lausanne
Publisher: Frontiers Media S.A.
Journal or Publication Title: Frontiers in Immunology
Volume of the journal: 11
Collation: 15 Seiten
DOI: 10.26083/tuprints-00017467
Corresponding Links:
Origin: Secondary publication DeepGreen

The B-cell receptor (BCR) is a key player of the adaptive immune system. It is a unique part of immunoglobulin (Ig) molecules expressed on the surface of B cells. In case of many B-cell lymphomas, the tumor cells express a tumor-specific and functionally active BCR, also known as idiotype. Utilizing the idiotype as target for lymphoma therapy has emerged to be demanding since the idiotype differs from patient to patient. Previous studies have shown that shark-derived antibody domains (vNARs) isolated from a semi-synthetic CDR3-randomized library allow for the rapid generation of anti-idiotype binders. In this study, we evaluated the potential of generating patient-specific binders against the idiotype of lymphomas. To this end, the BCRs of three different lymphoma cell lines SUP-B8, Daudi, and IM-9 were identified, the variable domains were reformatted and the resulting monoclonal antibodies produced. The SUP-B8 BCR served as antigen in fluorescence-activated cell sorting (FACS)-based screening of the yeast-displayed vNAR libraries which resulted after three rounds of screening in the enrichment of antigen-binding vNARs. Five vNARs were expressed as Fc fusion proteins and consequently analyzed for their binding to soluble antigen using biolayer interferometry (BLI) revealing binding constants in the lower single-digit nanomolar range. These variants showed specific binding to the parental SUP-B8 cell line confirming a similar folding of the recombinantly expressed proteins compared with the native cell surface-presented BCR. First initial experiments to utilize the generated vNAR-Fc variants for BCR-clustering to induce apoptosis or ADCC/ADCP did not result in a significant decrease of cell viability. Here, we report an alternative approach for a personalized B-cell lymphoma therapy based on the construction of vNAR-Fc antibody-drug conjugates to enable specific killing of malignant B cells, which may widen the therapeutic window for B-cell lymphoma therapy.

Uncontrolled Keywords: B-cell receptor, idiotype, lymphoma, yeast display, vNAR, antibody-drug conjugate
Identification Number: Artikel-ID: 560244
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-174678
Additional Information:

Specialty section: This article was submitted to B Cell Biology, a section of the journal Frontiers in Immunology

Classification DDC: 500 Science and mathematics > 540 Chemistry
500 Science and mathematics > 570 Life sciences, biology
600 Technology, medicine, applied sciences > 610 Medicine and health
Divisions: 07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie
Date Deposited: 12 Mar 2024 13:07
Last Modified: 18 Jul 2024 14:04
SWORD Depositor: Deep Green
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/17467
PPN: 519915593
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