The development of non-animal-based bioassays for cytokines and growth factors.

Abstract

Cytokines (including growth factors) exist as a family of proteins that possess a vast array of pleiotropic biological activities and therapeutic potential. As with any biological therapeutic, appropriate assessment of biological potency is vital to the development of cytokines as medicinal products. In early investigations of cytokine activity, in vivo bioassays were used to assess the whole body effects of cytokines in animals. The identification of the cellular targets of each cytokine allowed the extraction of tissue and the use of cells to produce in vitro bioassays, with the drastic reduction in the number of animals required. The discovery of cytokine-responsive tumours introduced a range of immortal, homogeneous tumour cell lines that are dependent on cytokines for proliferation. This allows cell lines to be made available for general distribution to laboratories internationally for bioassays, without the need for animals. More recently, the use of recombinant DNA technology to clone the specific receptor for the cytokine required for bioassay into an unresponsive cell line has led to a highly specific 'receptor-transduced' cell line. The most recent advances include the development of receptor signalling-based biochemical bioassays for cytokines.