The specific aims of this proposal are: 1) To determine if liposomes containing Interleukin 1 on their outer membranes may be used as synthetic macrophages to present antigen to lymphocytes, initiate the lymphokine cascade, kill IL 1-sensitive tumor cells, and stimulate the growth of IL 1- responsive cells. 2) To evaluate the biological activity of IL 1-liposomes in vivo for the ability to initiate the sequelae of inflammation, to induce angiogenesis, and to inhibit the growth and metastasis of tumors. 3) To elucidate the molecular mechanisms of macrophage activation which lead to induction and translation of IL 1-specific mRNA and to evaluate the effects of specific inhibitors of macrophage activation. 4) To determine the series of post-translational intracellular events which lead to the secretion of IL 1 from the monocyte and the deposition and anchoring of IL 1 in the membrane. 5) To further evaluate synthetic peptides which have been demonstrated to inhibit the biological activity of human IL 1.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038043-06
Application #
3176053
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1984-07-01
Project End
1992-05-31
Budget Start
1989-06-01
Budget End
1990-05-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Hospitals
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Saito, M; Fan, D; Lachman, L B (1995) Antitumor effects of liposomal IL1 alpha and TNF alpha against the pulmonary metastases of the B16F10 murine melanoma in syngeneic mice. Clin Exp Metastasis 13:249-59
Cabeza-Arvelaiz, Y; Shih, L C; Hardman, N et al. (1993) Cloning and genetic characterization of the human kinesin light-chain (KLC) gene. DNA Cell Biol 12:881-92
Bakouche, O; Moreau, J L; Lachman, L B (1992) Secretion of IL-1: role of protein kinase C. J Immunol 148:84-91
Bakouche, O; Moreau, J L; Lachman, L B (1992) Induction of IL-1: independent production of IL-1 alpha and IL-1 beta. Cytokine 4:106-13
Bakouche, O; Moreau, J L; Lachman, L B (1991) Acylation of cell-associated IL-1 by palmitic acid. J Immunol 147:2164-9
Bakouche, O; Lachman, L B (1990) Antigen presentation by liposomes bearing class II MHC and membrane IL-1. Yale J Biol Med 63:95-107
Bakouche, O; Lachman, L B (1990) Synthetic macrophages: liposomes bearing antigen, class II MHC and membrane-IL-1. Lymphokine Res 9:259-81
Bakouche, O; Lachman, L B (1989) Synthetic macrophages: antigen presentation by liposomes bearing class II major histocompatibility complex (MHC) and membrane interleukin-1 (IL-1). J Clin Immunol 9:369-77
D'Souza, R; Brown, L R; Newland, J R et al. (1989) Detection and characterization of interleukin-1 in human dental pulps. Arch Oral Biol 34:307-13
Gottlieb, R A; Lennarz, W J; Knowles, R D et al. (1989) Synthetic peptide corresponding to a conserved domain of the retroviral protein p15E blocks IL-1-mediated signal transduction. J Immunol 142:4321-8

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