TY - JOUR
T1 - Low dose subcutaneous interleukin-2 after autologous bmt safely augments NK activity
AU - Miller, J. S.
PY - 1996/12/1
Y1 - 1996/12/1
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:33748626927
VL - 24
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 9
ER -