Exogenous and endogenous tumour necrosis factor therapy.

Area of Science:

• Immunology
• Developmental Biology
• Oncology

Background:

• Tumour necrosis factor (TNF) is recognized for its tumoricidal properties.
• TNF also plays a crucial role in maintaining physiological homeostasis through an inflammation-like state.
• High concentrations of TNF are secreted by mouse embryonal cells, suggesting a role in ontogenesis.

Purpose of the Study:

• To investigate the role of TNF in ontogenesis and homeostasis.
• To explore the therapeutic potential of inducing endogenous TNF for treating chronic diseases, including cancer.
• To develop novel strategies for localized TNF delivery and synergistic therapeutic effects.

Main Methods:

• Observation of TNF secretion in mouse embryonal cells during development.
• Development of methods to induce endogenous TNF production in adult subjects.
• Construction and utilization of a novel recombinant TNF variant (rTNF-S) for targeted delivery.
• Development of exogenous/endogenous TNF therapy (EET therapy) for synergistic tumor treatment.

Main Results:

• Identified a high TNF concentration state during development termed 'ontogenic inflammation'.
• Demonstrated that inducing endogenous TNF can restore homeostasis and potentially cause tumor regression.
• Established the critical importance of TNF localization around tumor lesions for effective therapy.
• Exogenous/endogenous TNF therapy (EET therapy) showed synergistic effects by targeting TNF to tumors.

Conclusions:

• Ontogenic inflammation, mediated by TNF, is crucial for maintaining homeostasis in both developing and adult organisms.
• Targeted induction and delivery of TNF, as in EET therapy, offer a promising approach for cancer treatment.
• Ontogenic inflammation strategies may also be beneficial for treating other conditions like rheumatism.