A hybrid fever therapy for increased tumor selectivity

Area of Science:

• Oncology
• Immunology
• Biomedical Engineering

Background:

• Lipopolysaccharide (LPS) is a potent endotoxin with therapeutic potential, but its clinical use is limited by severe side effects like sepsis.
• Tumors exhibit elevated granulocyte-colony stimulating factor (G-CSF) and neutrophil concentrations, offering a potential target for localized therapy.

Purpose of the Study:

• To investigate a hybrid therapeutic approach combining moderate hyperthermia and low-dose LPS for selective tumor treatment.
• To explore the potential for inducing a localized sepsis-like syndrome within malignant tissues to achieve tumor necrosis and regression.

Main Methods:

• Exploiting elevated G-CSF and neutrophil levels within tumors.
• Applying moderate hyperthermia and low-dose lipopolysaccharide (LPS).
• Monitoring biomarkers such as heat shock proteins, circulating endothelial cells, and intravital microscopy of intravascular neutrophil extracellular traps (NETs), microthrombi, and bleeding.

Main Results:

• The proposed method aims to selectively trigger a sepsis-like syndrome in malignant tissues, sparing normal organs.
• Repeated application is predicted to induce tumor necrosis and regression.
• Biomarkers will be used to validate the predicted therapeutic consequences.

Conclusions:

• A hybrid approach of hyperthermia and mild endotoxemia offers a tumor-specific therapeutic modality.
• This approach may have relatively mild side effects, allowing for repeated application.
• The strategy holds promise for extended treatment periods in cancer therapy.