Header

UZH-Logo

Maintenance Infos

A novel dual-cytokine-antibody fusion protein for the treatment of CD38-positive malignancies


De Luca, Roberto; Kachel, Paul; Kropivsek, Klara; Snijder, Berend; Manz, Markus G; Neri, Dario (2018). A novel dual-cytokine-antibody fusion protein for the treatment of CD38-positive malignancies. Protein Engineering, Design & Selection, 31(5):173-179.

Abstract

A novel dual-cytokine-antibody fusion protein, consisting of an antibody directed against CD38 [a tumor-associated antigen mainly expressed on the surface of multiple myeloma (MM) cells], simultaneously fused to both tumor necrosis factor ligand superfamily member 10 (TRAIL) and interleukin-2 (IL2), was designed, expressed and purified to homogeneity. The novel fusion protein, termed IL2-αCD38-αCD38-scTRAIL, was able to selectively recognize its cognate antigen expressed on the surface of MM and lymphoma cell lines, as evidenced by flow cytometry analysis. Moreover, the targeted version of TRAIL was able to induce cancer cell death in vitro, both with MM cell lines and with fresh isolates from the bone marrow of MM patients. The experiments provide a rationale for possible future applications of IL2-αCD38-αCD38-scTRAIL for the treatment of patients with MM or other CD38-positive malignancies.

Abstract

A novel dual-cytokine-antibody fusion protein, consisting of an antibody directed against CD38 [a tumor-associated antigen mainly expressed on the surface of multiple myeloma (MM) cells], simultaneously fused to both tumor necrosis factor ligand superfamily member 10 (TRAIL) and interleukin-2 (IL2), was designed, expressed and purified to homogeneity. The novel fusion protein, termed IL2-αCD38-αCD38-scTRAIL, was able to selectively recognize its cognate antigen expressed on the surface of MM and lymphoma cell lines, as evidenced by flow cytometry analysis. Moreover, the targeted version of TRAIL was able to induce cancer cell death in vitro, both with MM cell lines and with fresh isolates from the bone marrow of MM patients. The experiments provide a rationale for possible future applications of IL2-αCD38-αCD38-scTRAIL for the treatment of patients with MM or other CD38-positive malignancies.

Statistics

Citations

Dimensions.ai Metrics
1 citation in Web of Science®
1 citation in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:5 July 2018
Deposited On:05 Sep 2018 14:23
Last Modified:24 Sep 2019 23:35
Publisher:Oxford University Press
ISSN:1741-0126
OA Status:Closed
Free access at:Related URL. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/protein/gzy015
Related URLs:https://academic.oup.com/peds/advance-article/doi/10.1093/protein/gzy015/5049168 (Publisher)
PubMed ID:29982719

Download

Full text not available from this repository.
View at publisher

Get full-text in a library