Assessment of Choline Dihydrogen Phosphate (CDHP) As a Vehicle for Recombinant Human Interleukin-2 (rhIL-2)

Overview

Journal Cell Mol Bioeng

Publisher Springer

Specialty Biomedical Engineering

Date 2014 Feb 8

PMID 24504148

Citations 6

Authors

David M Foureau

Regina M Vrikkis

Chase P Jones

Katherine D Weaver

Douglas R MacFarlane

Jonathan C Salo

Iain H McKillop

Gloria D Elliott

Affiliations

Soon will be listed here.

Abstract

Choline dihydrogen phosphate (CDHP) is an ionic liquid reported to increase thermal stability of model proteins. The current work investigated CDHP effect on structural integrity and biological activity of recombinant human interleukin-2 (rhIL-2), a therapeutic protein used for treating advanced melanoma. CDHP biocompatibility was also evaluated using primary cell cultures, or B16-F10 cell line, chronically exposed to the ionic liquid. Formulation of rhIL-2 in an aqueous 680mM CDHP pH 7.4 solution resulted in a 12.5°C increase in the T of rhIL-2 compared to a basic buffer formulation, and provided conformational rhIL-2 stabilization when the solution was heated to 23.3°C above the T. CDHP solutions (≤80mM), exhibited no cytotoxic activity toward primary splenocytes or B16-F10 cells in culture. However, a 10-fold loss in biological activity was observed when rhIL-2 was used in a 30mM CDHP aqueous solution with NaHCO (pH≥7.2) compared to controls without CDHP. While increased T is associated with a diminished rhIL-2 biological activity, the therapeutic protein remains structurally intact and functional.

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