CONJUGATES TARGETED TO TARGET RECEPTORS

摘要

A conjugate for intracellular delivery of a chemical agent into a target receptor such as an 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 endocytosis-inducing ligand coupled to a water soluble polymer. The ligand binds to a target receptor such as an IL-2 receptor on the target receptor bearing cell and elicits endocytosis of the conjugate. The conjugate 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. Methods of using these compositions for delivering a chemical agent in vivoor in vitro are also disclosed. Methods 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 also are disclosed.