The goal of this project is to develop a target specific drug delivery system to cells which have been infected with Human Immunodeficiency Virus. The specific delivery vehicles to be used in the project are immunoliposomes which contain covalently conjugated monoclonal antibody to specific antigenic sites on the surface of the infected cells. As an initial step, we will use two animal models to evaluate our approach. The first is T- lymphocytes which have been infected in vitro by recombinant murine leukemia virus containing the Herpes Simplex Virus glycoprotein gD gene. Since the virus will be so constructed that it is infectious but not replication competent, HSV-gD will be constitutively expressed on the surface of the infected T-cells. These cells will be injected inot syngenic mice to serve as a target for immunoliposomes containing anti-HSV-gD. Elimination of these cells in the circulation by cytotoxic drugs (such as ara C) encapsulated in the immunoliposomes is expected. Another animal model is cats which have been persistently infected with the Feline Leukemia Virus. Immunoliposomes containing anti- FLV-gp70 will be used to target cytotoxic or antiviral drugs to the infected cells. Two types of immunoliposomes will be used: the pH-sensitive immunoliposome which effectively delivers drugs to the cytoplasm of the target cells via the endocytosis pathway, and the target-sensitive immunoliposome which spontaneously releases drugs at the target cell surface. Liposome targeting and drug delivery will be studied first in vitro to obtain optimal conditions for liposome stability, drug entrapment, binding to cells, drug delivery and cell killing. Extensive animal work will then follow.
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