DELIVERY OF INTERLEUKIN-2 FOR IMMUNOTHERAPY

The local production of interleukin 2 (IL-2) by T lymphocytes acts to enhance the immune response by inducing growth and differentiation of a variety of immune cells. In clinical situations that require immunostimulation, such as vaccination and enhancement of tumor immunity, IL-2 therapy has been considered; however, the extraordinary toxicity of the drug inoculated systemically has greatly limited its application. Since the most serious toxic consequences of the drug are related to its systemic delivery, alternative strategies have been developed. Local delivery of the cytokine has been successfully used in some circumstances, and this form of delivery does not result in the life-threatening complications that limit systemic use. Liposome encapsulated IL-2 represents a mechanism to accentuate local delivery by causing a depot effect. Finally, the use of IL-2 has been predicated on the conception of the cytokine as an absolute monomer. Nevertheless, IL-2 spontaneously forms noncovalent and covalent self-associations. Because covalent dimers have been shown to initiate differential signalling in target cells, it is necessary to account for this property in devising and evaluating therapeutic protocols; moreover, it seems possible to use this property for modifying and regulating the therapeutic response.