Intravenous ascorbic acid as an adjuvant to interleukin-2 immunotherapy

Area of Science:

• Oncology
• Immunology
• Biochemistry

Background:

• Interleukin-2 (IL-2) therapy shows efficacy in advanced melanoma and renal cell carcinoma but is limited by severe toxicity.
• IL-2 therapy is associated with significant drops in circulating ascorbic acid (AA) levels.
• IL-2 toxicity shares features with sepsis, including capillary leakage and inflammatory mediator release.

Purpose of the Study:

• To present a scientific rationale for evaluating intravenous ascorbic acid (AA) as an adjuvant therapy.
• To explore AA's potential to mitigate IL-2-mediated toxicity.
• To investigate if AA can enhance the efficacy of IL-2 treatment.

Main Methods:

• Review of existing literature on IL-2 therapy, toxicity mechanisms, and ascorbic acid's role in sepsis.
• Analysis of shared pathophysiological features between IL-2 toxicity and sepsis.
• Consideration of AA's known biological activities, including antitumor effects.

Main Results:

• IL-2 therapy induces significant depletion of circulating AA.
• AA depletion in sepsis models is linked to disease severity and improved with AA administration.
• AA possesses independent antitumor properties, including cytotoxicity and anti-angiogenesis.

Conclusions:

• Intravenous AA is proposed as a potential adjuvant to reduce IL-2 toxicity.
• AA may offer a dual benefit by decreasing toxicity and potentially enhancing IL-2's therapeutic effects.
• Further clinical assessment of AA as an adjuvant to IL-2 therapy is warranted.