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Design and characterisation of a novel interleukin-15 receptor alpha fusion protein and analysis of interleukin-15 complexation.


ABSTRACT: Interleukin-15 (IL15) is one of the most important cytokines currently being considered for cancer therapy applications. It is thought that by administering IL15 in complex with its cognate receptor alpha chain (IL15R?) its biological activity could be increased manifold. We produced a fusion protein of mouse IL15R? and the F8 antibody, that targets the alternatively-spliced extra-domain A (EDA) of fibronectin, which is overexpressed in many types of cancer. The fusion protein F8IL15R? was cloned, expressed and characterized in vitro and its ability to bind to mouse IL15 was assessed with both size exclusion chromatography (SEC) and surface plasmon resonance (SPR) experiments. Furthermore, mouse and human IL15 and their corresponding Fc fused IL15R? subunits were purchased, characterized and used to compare the capacity of F8IL15R? to generate complexes. Surprisingly, none of the IL15R? fusion proteins showed IL15 complexation on SEC. However, on SPR, F8IL15R? displayed the ability to bind IL15. In a cell-based activity assay none of the IL15R? fusions were able to increase cellular proliferation in combination with IL15 compared to IL15 alone. A better understanding of the molecular requirements for effective IL15 signalling are likely to be important for the development of IL15-based biopharmaceuticals.

SUBMITTER: Schmid AS 

PROVIDER: S-EPMC6660064 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Design and characterisation of a novel interleukin-15 receptor alpha fusion protein and analysis of interleukin-15 complexation.

Schmid Anja Sophie AS   Neri Dario D  

PloS one 20190726 7


Interleukin-15 (IL15) is one of the most important cytokines currently being considered for cancer therapy applications. It is thought that by administering IL15 in complex with its cognate receptor alpha chain (IL15Rα) its biological activity could be increased manifold. We produced a fusion protein of mouse IL15Rα and the F8 antibody, that targets the alternatively-spliced extra-domain A (EDA) of fibronectin, which is overexpressed in many types of cancer. The fusion protein F8IL15Rα was clone  ...[more]

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