Talactoferrin stimulates wound healing with modulation of inflammation.

Background: Inflammation is an acute, early process during normal wound healing. Talactoferrin, a recombinant human lactoferrin, can induce the secretion of inflammatory mediators.

Materials And Methods: We measured wound healing activity of topical talactoferrin in full-thickness wounds of normal mice and diabetic (db(-)/db(-)) mice, systemic bioavailability, and the potential to modulate inflammation through in vitro and in vivo binding assays and inflammatory mediator measurements.

Requirement for IFN-gamma, CD8+ T lymphocytes, and NKT cells in talactoferrin-induced inhibition of neu+ tumors.

We have previously shown that talactoferrin-alfa (TLF), a recombinant human lactoferrin, is an immunomodulatory protein that is active against implanted tumors, both as a single agent and in combination with chemotherapy. In this study, we show that talactoferrin is active against autochthonous tumors in a transgenic mouse line, which is more analogous to human cancers, and identify key mechanistic steps involved in the anticancer activity of oral TLF. BALB/c mice transgenic for the rat neu (ErbB2) oncogene (BALB-neuT) treated with oral TLF showed a significant delay in carcinogenesis, with 60% tumor protection relative to vehicle-treated mice at week 21.

Intravenous delivery of an endostatin gene complexed in cationic lipid inhibits systemic angiogenesis and tumor growth in murine models.

Inhibition of the neovascularization of tumors has proven efficacious in reducing tumor growth and metastases. Attaining antiangiogenesis through cationic lipid-based systemic gene therapy presents an attractive approach to the treatment of disseminated and primary cancers. Intravenous administration of an endostatin plasmid, complexed with a cationic lipid system, produced significant levels of endostatin in the lung and the circulation.

Intratracheal administration of interleukin 12 plasmid-cationic lipid complexes inhibits murine lung metastases.

Administration of plasmid/lipid complexes to the lung airways for the treatment of metastatic pulmonary diseases represents a new strategy of gene therapy. In this study we present evidence that intratracheal administration of a plasmid encoding murine IL-12 complexed with N-[1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride:cholesterol inhibits the growth of lung metastases, using a renal cell carcinoma model. Instillation of pIL-12/lipid complexes resulted in expression of biologically active IL-12 (170-240 pg/ml) and IFN-gamma (100-190 pg/ml) in the bronchoalveolar lavage fluid.

Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene.

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of angiostatic factors should be a viable approach for cancer gene therapy. Endostatin, a potent angiostatic factor, was expressed in mouse muscle and secreted into the bloodstream for up to 2 weeks after a single intramuscular administration of the endostatin gene.