Life-prolonging effect of immunocell BAK (BRM-activated killer) therapy for advanced solid cancer patients: prognostic significance of serum immunosuppressive acidic protein levels.
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.
Ebina
Takusaburo
T
Division of Immunology, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-shiode, 981-1293 Natori, Miyagi, Japan. takebina@mcc.pref.miyagi.jp
Ogama
Naoko
N
Shimanuki
Hiroko
H
Kubota
Tomoka
T
Isono
Noriko
N
D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000276:immunology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D010865:Pilot Projects; D011379:Prognosis; D011788:Quality of Life; D016019:Survival Analysis
D019002:CD56 Antigen; D009363:Neoplasm Proteins; C030193:immunosuppressive acidic protein