Tumor Integrin-Targeted Glucose Oxidase Enzyme Promotes ROS-Mediated Cell Death that Combines with Interferon Alpha...

Area of Science:

• Biochemistry
• Immunology
• Oncology

Background:

• Reactive oxygen species (ROS) typically suppress tumors but can eliminate them.
• Cancer treatments can increase ROS, affecting cell death and immune recognition.
• Myeloid cells use ROS to fight pathogens and, increasingly, cancer.

Purpose of the Study:

• To explore glucose oxidase as a therapeutic to mimic myeloid ROS bursts.
• To engineer glucose oxidase for tumor-specific targeting and prolonged activity.
• To assess its potential in initiating antitumor immune responses and synergizing with immunotherapy.

Main Methods:

• Engineered glucose oxidase targeting pan-tumor integrins.
• In vitro assessment of cancer cell death and dendritic cell cross-presentation.
• In vivo studies in murine MC38 tumors combined with interferon alpha therapy.

Main Results:

• Targeted glucose oxidase induced potent cancer cell death in vitro.
• Enhanced cross-presentation by dendritic cells was observed.
• Combination therapy achieved long-term tumor control in vivo with optimized single-dose administration.
• Overcame immunogenicity issues associated with other prooxidant enzymes.

Conclusions:

• ROS-induced cancer cell death can be therapeutically harnessed for tumor control.
• Designed enzyme therapies targeting ROS show potential for cancer treatment.
• This approach may synergize with current immunotherapies for improved solid tumor outcomes.