CONJUGATES TARGETED TO THE INTERLEUKIN-2 RECEPTORS

摘要

A composition for intracellular delivery of a chemical agent into a target receptor and/or interleukin-2-receptor-bearing cell, e.g. an activated T cell and cancer cell, includes a chemical agent, at least one copy of target-receptor binding and/or an interleukin-2-receptor-binding and endocytosis-inducing ligand coupled to a water soluble polymer. The ligand binds to a target receptor and/or IL-2 receptor on the target receptor and/or IL-2-receptor-bearing cell and elicits endocytosis of the composition. The composition also optionally includes a biodegradable spacer for coupling the chemical agent and the ligand to the polymer. Chemical agents can include cytotoxins, transforming nucleic acids, gene regulators, labels, antigens, drugs, and the like. A preferred water soluble polymer is polyalkylene oxide, such as polyethylene glycol and polyethylene oxide, and activated derivatives thereof. The composition can further comprise a carrier such as another water soluble polymer, liposome, or particulate. Methods of using these compositions for delivering a chemical agent in vivo or in vitro are also disclosed. A method of detecting a disease, such as cancer, T-cell lymphocytic leukemia, T-cell acute lymphoblastic leukemia, peripheral T-cell lymphoma, Hodgkin's disease, and non-Hodgkin's lymphoma, associated with elevated levels of soluble target receptor and/or IL-2 receptor is also disclosed.