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. Pe ripheral blood lymphocytes were selected by immobilization with anti-CD3 mo noclonal antibody and cultured for 2 weeks in the presence of IL-2. Thereaf ter, they were reactivated by 1,000 U/ml of IFN-alpha for 15 min. Twenty-si x outpatients with cancer whose performance status were over 80% on Karnofs ky scale were selected for this study. About 6 x 10 degrees BAK cells were returned by intravenous drip infusion, at one month intervals at an outpati ent clinic to each of 20 advanced cancer patients in whom many metastatic l esions were found postoperatively, and to 6 patients with no postoperativel y detectable metastases, The proportion of CD56-positive cells increased fr om 20% to 50% with culture, CD56-positive cells have strong cytotoxic activ ity and produced 20 ng/10 degrees cells of beta -endorphin, an intrarerebra l 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 fell well and maintains good Q OL 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 th at the CD56-positive cell is a multifunctional, integrated NIE: (neuro-immu ne-endocrine) cell. Administration of BAK cells allowed all 20 advanced can cer patients with metastases to survive for over one year. All 6 patients r eceiving the same therapy for prevention of postoperative metastasis have b een recurrence-free for one to five years.