Effector mechanism and clinical response of BAK (BRM-activated killer) immuno-cell therapy for maintaining satisfactory QOL of advanced cancer patients utilizing CD56-positive NIE (neuro-immune-endocrine) cells.
A new type of immuno-cell therapy called BRM-activated killer (BAK) therapy using non-MHC-restricted lymphocytes, CD56-positive cells, was devised. Peripheral blood lymphocytes were selected by immobilization with anti-CD3 monoclonal antibody and cultured for 2 weeks in the presence of IL-2. Thereafter, they were reactivated by 1,000 U/ml of IFN-alpha for 15 min. Twenty-six outpatients with cancer whose performance status were over 80% on Karnofsky scale were selected for this study. About 6 x 10(9) BAK cells were returned by intravenous drip infusion, at one month intervals at an outpatient clinic to each of 20 advanced cancer patients in whom many metastatic lesions were found postoperatively, and to 6 patients with no postoperatively detectable metastases. The proportion of CD56-positive cells increased from 20% to 50% with culture. CD56-positive cells have strong cytotoxic activity and produced 20 ng/10(9) cells of beta-endorphin, an intracerebral hormone. During the course of BAK therapy, we adopted the Face scale as a QOL indicator. The QOL of all patients remained satisfactory or improved. Beta-endorphin is thought to make patients feel well and maintains good QOL because of its potent analgesic, sedative activity. From that facts that CD56 is a neural cell adhesion molecule and a member of the Ig superfamily, and that the CD56-positive cell produces beta-endorphin, we concluded that the CD56-positive cell is a multifunctional, integrated NIE (neuro-immune-endocrine) cell. Administration of BAK cells allowed all 20 advanced cancer patients with metastases to survive for over one year. All 6 patients receiving the same therapy for prevention of postoperative metastasis have been recurrence-free for one to five years.
Ebina
T
T
Division of Immunology, Niyagi Cancer Center Research Institute, Natori, Japan. takebina@mcc.pref.miyagi.jp
Ogama
N
N
Shimanuki
H
H
Kubota
T
T
Isono
N
N
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000737:chemistry; D019002:CD56 Antigen; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007155:Immunologic Factors; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011379:Prognosis; D011788:Quality of Life; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D001615:beta-Endorphin / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D019002:CD56 Antigen; D007155:Immunologic Factors; D016898:Interferon-alpha; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D001615:beta-Endorphin; D007371:Interferon-gamma