Current biotherapy using old BRM and combined cytokines against cancer

Since the concept of BRM was proposed, OK-432, attenuated Streptococcus pyogenes, is classified into the group of old BRM, and cytokines such as IFN and TNF are classified into the group of new BRM. Recently, it has become clearer that old BRM is a multiple-cytokine inducer and a sort of biochemical modulator. Based on this, the clinical significance of preoperative intratumoral injection of OK-432 and the combination therapy with IFN and TNF are herein reported. The injection of OK-432, 7~10 days before operation, significantly improved the 5-year survival rate of patients with stage III gastric cancer, and had a particular positive effect in the cases showing marked tumor infiltrating lymphocytes. The combined use of natural human interferon-α and natural human tumor necrosis factor-α causes a synergistic enhancement of antitumor effect both in vitro and in vivo. In an early phase II clinical trial, out of 72 cases with advanced or recurrent cancer receiving more than 2 x 10⁶ U/day, four cases had CR, ten had PR and four had MR. The response rate was 19.4%, and responsive cancers were hepatoma, renal cell cancer, breast cancer, ovarian cancer and so on. Two of four cases with CR survive still more than 6 years without recurrence. Two to 4 x 10⁶ U/day is possible to administer for a long time without severe side effects. Preoperative intratumoral injection of old BRM and combined use of cytokines are thought to be a promising antitumor therapy.