title: Intravenous ascorbic acid as an adjuvant to interleukin-2 immunotherapy.
abstract: Interleukin-2 (IL-2) therapy has been demonstrated to induce responses in 10-20% of advanced melanoma and renal cell carcinoma patients, which translates into durable remissions in up to half of the responsers. Unfortunately the use of IL-2 has been associated with severe toxicity and death. It has been previously observed and reported that IL-2 therapy causes a major drop in circulating levels of ascorbic acid (AA). The IL-2 induced toxicity shares many features with sepsis such as capillary leakage, systemic complement activation, and a relatively non-specific rise in inflammatory mediators such as TNF-alpha, C-reactive protein, and in advanced cases organ failure. Animal models and clinical studies have shown rapid depletion of AA in conditions of sepsis and amelioration associated with administration of AA (JTM 9:1-7, 2011). In contrast to other approaches to dealing with IL-2 toxicity, which may also interfere with therapeutic effects, AA possesses the added advantage of having direct antitumor activity through cytotoxic mechanisms and suppression of angiogenesis. Here we present a scientific rationale to support the assessment of intravenous AA as an adjuvant to decrease IL-2 mediated toxicity and possibly increase treatment efficacy.
authors.affiliation: Batu Biologics, San Diego, California, USA. samuel.wagner@batubiologics.com.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Wagner
authors.forename: Boris
authors.initials: B
authors.lastname: Markosian
authors.forename: Naseem
authors.initials: N
authors.lastname: Ajili
authors.forename: Brandon R
authors.initials: BR
authors.lastname: Dolan
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Kim
authors.forename: Doru T
authors.initials: DT
authors.lastname: Alexandrescu
authors.forename: Constantin A
authors.initials: CA
authors.lastname: Dasanu
authors.forename: Boris
authors.initials: B
authors.lastname: Minev
authors.forename: James
authors.initials: J
authors.lastname: Koropatnick
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Neil H
authors.initials: NH
authors.lastname: Riordan
mesh_terms: D001205:Ascorbic Acid / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use*; D018384:Oxidative Stress
chemical_list: D007376:Interleukin-2; D001205:Ascorbic Acid