Low dose subcutaneous interleukin-2 after autologous bmt safely augments NK activity

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Autologous BMT (ABMT) can induce long term disease control in patients with advanced breast cancer and lymphoma yet nearly 80% and 50%, respectively, will ultimately relapse. In vitro studies suggest that activated NK cells, but not CD4+ or CD8+ T-cells, mediate lytic activity against breast cancer and lymphoma cell lines. Eleven évaluable patients (5 lymphoma, 6 breast cancer) were enrolled on a phase I dose escalation study after ABMT (median day + 94, range 50-166). IL-2 (Amgen) was self administered at 0.25 x 106 (n=5) or 0.5 x 106 (n=6) IU/m2 s.c. daily for 84 consecutive days. The best tolerated dose was 0.25 x 106 IU/m2 {78% of planned doses given vs. 56% at the higher dose). Dose limiting toxicity occurred in 5 patients (I at0.25x 106,4atO,5x 106) consisting of decreased performance status (n=l), thrombocytopenia (n=3, 1 at the lower dose), and mild weight gain and constitutional symptoms (n=l). Despite this toxicity, all symptoms resolved within a week off IL-2. No patient required hospitalization for toxicity related to IL-2. All patients receiving at least 28 days of IL-2 exhibited a > 10-fold increment in absolute circulating CD56+/CD3- NK. The median absolute NK count/cc blood was 1770 ner mm3 of which >SO% coexnressed CDS and CDIfi. In addition to in vivo expansion of NK, lytic function was increased against Raji (lymphoma) and MCF-7 (breast cancer) which was enhanced further by overnight ex vivo activation in 1000 IU/ml IL-2. In vivo IL-2 primed NK can be activated ex vivo at high cell density (10 x lO/ml) in gas permeable bags using serum free media. Cellular immunotherapy to maximize NK function to prevent relapse will be tested after ABMT in breast cancer and lymphoma.

Original languageEnglish (US)
Number of pages1
JournalExperimental Hematology
Issue number9
StatePublished - Dec 1 1996

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