Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors

Area of Science:

• Oncology
• Immunology
• Enzymology

Background:

• Extracellular adenosine suppresses anti-tumor immunity and promotes tumor progression.
• The role of Adenosine deaminase 2 (ADA2) in cancer and its therapeutic potential remains unexplored.

Purpose of the Study:

• To investigate the role of ADA2 in cancer.
• To evaluate ADA2 as a potential cancer immunotherapy targeting adenosine.

Main Methods:

• Assessed ADA2 expression in relation to patient survival and immune response pathways in solid tumors.
• Engineered ADA2 variants with improved catalytic efficiency.
• Developed PEGylated ADA2 (PEGADA2) for prolonged systemic exposure.
• Evaluated PEGADA2 efficacy in mouse tumor models.

Main Results:

• Increased ADA2 expression correlated with improved patient survival and enhanced adaptive immune responses.
• PEGADA2 demonstrated significant tumor growth inhibition in mice.
• Inhibition was dependent on enzyme activity and modulated immune responses.
• Adenosine targeting by PEGADA2 was confirmed as the mechanism of action.

Conclusions:

• Endogenous ADA2 expression serves as a prognostic biomarker for cancer patient survival.
• Engineered ADA2, specifically PEGADA2, represents a novel enzymatic immunotherapy for cancer by targeting extracellular adenosine.