Endogenous substances as drugs. Issues related to the application of cytokines in cancer therapy

Cytokines are the protein products of cells which regulate proliferation, differentiation and functional activation. The potent biological properties of these proteins have led to their introduction into clinical medicine as pharmacological agents. The cytokines most studied to date include the interferons, some of the interleukins and the haematopoietic growth factors. Although they have most often been studied in cancer patients, widespread application of these agents in many other fields is likely. Despite the fact that these are recombinant proteins of defined sequence, their intricate biology complicates clinical investigation. Proteins may be of native or mutated sequence and their degree of glycosylation is further affected by the expression system used for their production. Furthermore, although these cytokines interact with specific cell surface receptors, pleotropic biological consequences may follow from the interaction of ligand with receptors. As a consequence, significant dose and schedule dependency exists for these agents, and the particular administration regimen as well as the route of delivery may greatly affect the biological and clinical characteristics of these drugs. Thus, direct comparisons of different cytokine problems may be difficult. These issues reinforce the need for increased biological understanding of cytokines if these agents are to be used rationally and safely in clinical medicine.