We devised an innovative type of immunocell
therapy called BRM (
biological response modifier)-activated killer (BAK)
therapy, which utilizes most of non-MHC (major histocompatibility complex) restricted lymphocytes, CD56+ cells including gammadelta T cells and NK cells. Peripheral blood lymphocytes were selected by immobilizing them with anti-CD3
monoclonal antibody, cultured for 2 weeks with serum-free medium containing
IL-2, and then were reactivated by 1,000 U/ml of IFN-alpha for 15 min. The patients were infused with about 6x10(9) BAK cells by
intravenous drip infusion at 1-month intervals. All advanced solid
cancer patients who had received
chemotherapy but for whom it was not effective or have refused
chemotherapy were included in the present study. A good marker of impairment of host immune response by
chemotherapy is an
immunosuppressive acidic protein (IAP) level in serum above 580 microg/ml; survival rates were compared with the high (> 580 microg/ml) and the low (< or = 580 microg/ml) serum IAP groups. We enrolled in this study 23 immunosuppressed patients whose IAP levels in serum were over 580 microg/ml, and 42 immunoreactive solid
cancer outpatients whose IAP level in serum were under 580 degreesg/ml and whose performance statuses were over 80% on the Karnofsky scale. After giving informed consent, patients were treated with BAK
therapy on an outpatient basis at our hospital. The ethical review board of the Miyagi
Cancer Center approved this pilot study. Treated with BAK
therapy, the mean survival of immunosuppressed patients was 4.6 months. On the other hand, survival for one of immunoreactive advanced postoperative patients (stage IV) and inoperable
lung cancer patients (stage IIIb) was 24.7 months. The difference in survival between the 2 groups was significant (P < 0.01). This shows that BAK
therapy is not indicated for an advanced
cancer patient whose serum IAP is over 580 microg/ml, perhaps due to extensive
chemotherapy. Overall response to BAK
therapy was complete response (CR) in 5 cases, partial response (PR) in 1 case, and prolonged no change (NC) in 26 cases, with an effectiveness rate at 76.2% in 42 advanced stage IIIb and IV
cancer patients. BAK
therapy has a life-prolonging effect without any adverse effects and maintains satisfactory quality of life (QOL) for advanced
cancer patients.