Adoptive immunotherapy of human cancer was investigated in our institution as part of a National Cancer Institute extramural group study. This treatment, for patients with metastatic malignant melanoma, hypernephroma, and colon carcinoma, consisted of three phases: (a) 5 days of i.v. high-dose (105 units/kg every 8 h) interleukin 2, (b) 6½ days of rest plus leukapheresis; and (c) 4 days of high-dose interleukin 2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Ascorbic acid is known to be important to cell-mediated immunity, and it has been reported to be depleted during physiologically stressful events. Therefore, we determined plasma ascorbic acid levels in patients (n = 11) before adoptive immunotherapy and before and after Phases 1, 2, and 3 of treatment. Patients entering the trial were not malnourished. Mean plasma ascorbic acid levels were normal (0.64 ± 0.25 mg/dl) before therapy. Mean levels dropped by 80% after the first phase of treatment with high-dose interleukin 2 alone (0.13 ± 0.08 mg/dl). Mean plasma ascorbic acid levels remained severely depleted (0.08 to 0.13 mg/dl) throughout the remainder of the treatment, becoming undetectable (<0.05 mg/dl) in eight of 11 patients during this time. Values obtained from 24-h urine collections on two of two patients indicated that ascorbate was not excreted in the urine. Plasma ascorbic acid normalized in three of three patients tested 1 mo after the completion of treatment. Unlike the results for ascorbic acid, blood pantothenate and plasma vitamin E remained within normal limits in all 11 patients throughout the phases of therapy. Responders (n = 3) differed from nonresponders (n = 8) in that plasma ascorbate levels in the former recovered to at least 0.1 mg/dl (frank clinical scurvy) during Phases 2 and 3, whereas levels in the latter fell below this level.
This work was supported, in part, by National Cancer Institute Grant CA 14958 (to P. H. W.) and by Cancer Center Core Grant CA 13330 to the Albert Einstein College of Medicine. A preliminary report of this work has been presented (19).