Posttransplant adoptive immunotherapy with activated natural killer cells in patients with metastatic breast cancer

Relapse after high-dose chemotherapy is the main cause of therapeutic failu re in patients with metastatic breast cancer. Adoptive immunotherapy with i nterleukin-2 (IL-2) plus activated natural killer cells may eliminate resid ual disease without excessive toxicity. The authors sought to determine if immunotherapy immediately after transplantation would affect engraftment an d the toxicity associated with transplantation. Fifteen consecutive patient s with metastatic breast cancer were allocated to three cohorts. Cohort 1 ( five patients) received high-dose cyclophosphamide, thiotepa, and carboplat in (CTCb) followed by peripheral blood stem cell infusion and granulocyte c olony-stimulating factor at 10 mu g/kg. Cohort 2 (five patients) received i n addition rhIL-2 (2 x 10(6) IU/m(2)/day) for 4 days intravenously via cont inuous infusion after peripheral blood stem cell infusion. In cohort 3 (fiv e patients), peripheral blood stem cell transplant was followed by infusion of autologous activated NK cells and rhIL-2 (2 x 10(6) IU/m2/day) for 3 da ys (via continuous intravenous infusion). Generation of activated NK cells was possible in all patients in cohort 3. All patients has successful engra ftment. Median time to absolute neutrophil count more than 0.5 x 10(9)/L wa s 8 days (range, 8 to 11 days) in cohort 1, 9 days (range, 7 to 11 days) in cohort 2, and 9 days (range, 8 to 9 days) in cohort 3. Median time until t he platelet count was more than 20 x 10(9)/L was 14 days (range, 9 to 22 da ys) in cohort 1, 11 days (range, 6 to 14 days) in cohort 2, and 12 days (ra nge, 11 to 21 days) in cohort 3, All patients developed neutropenic fevers, but the overall toxicity associated with the infusion of IL-2 (cohort 2) o r IL-2 plus activated NK cells (cohort 3) did not differ from that observed in cohort 1. Complete responses were achieved in one patient in cohort 1, in two patients in cohort 2, and in one patient in cohort 3. In conclusion, post-transplant adoptive immunotherapy with activated NK cells plus IL-2 i s feasible, well tolerated, and does not adversely affect engraftment.