This application proposes biological studies which will continue our previous work on human gamma (Gamma) interferon. This type of interferon was formerly referred to as """"""""immune"""""""" interferon or """"""""Type II"""""""" interferon.
The specific aims are (1) to charctarize the lymphocyte subsets of patients with accute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL), (in remission, off chemotherapy, and when possible, in relapse) in order to determine if the previously documented defincient Gamma interferon response of these patients' lymphocytes is due to a lymphopenia involving the Gamma-interferon producing subset, or due instead to a functional abnormality, and (2) to study whether enhancement of the antiviral, anticellular and immunomodulatory activities of Gamma interferon can be achieved by entrapping the interferon in lipid vesicles (liposomes). The role of liposome type, composition and size on interferon will be studied as well as the stability of the interferon-liposomes. The Gamma inteferon-liposomes will be compared to free Gamma interferon for: antiviral activity against herpesvirus 1 and 2, cytomegalovirus, and varicella-zoster; anticellular activity against cell lines of colon carcinoma, urinary bladder carcinoma, lung carcinoma, rhabdosarcoma, osteogenic sarcoma, and myelocytic leukemia; and immunomodulatory activity in systems which measure mitogen stimulation of lymphocytes, phagocytosis by macrophages, NK cell activity, and normal T and B cell functions. The long-term objectives of this study are (1) to determine the nature of the Gamma interferon deficiency which occurs in cells of patients with lymphocytic leukemia, and (2) to enhance the therapeutic effect of Gamma interferon as an antiviral, anticellular, and immunomodulatory agent.
| Smith, D M; Mayhew, E; Reszka, R et al. (1990) Antiviral and antiproliferative properties of liposome-associated human interferon-gamma. J Interferon Res 10:153-60 |
| Ito, M; O'Malley, J A (1987) Antiviral effects of recombinant human tumor necrosis factor. Lymphokine Res 6:309-18 |
