Majima H, Nomura K
Gan To Kagaku Ryoho. 1986 Jan;13(1):109-15.
MY-1 is the DNA fraction, isolated and purified from Mycobacterium bovis BCG, which is composed of water-soluble and heat-denatured nucleic acids. In preclinical study, MY-1 showed host-mediated antitumor activity against various kinds of syngeneic tumors, and revealed very low toxicity in animals. Since these results suggested that MY-1 could be used as a biological response modifier (BRM) for cancer therapy, we performed the phase I clinical study in patients with a variety of malignancies. Fifteen patients were treated using single s.c. injection of MY-1 at doses of 0.25-20 mg, and following 22 patients received 3-12.5 mg of MY-1 given s.c. 3 times a week for the period of 2 weeks. Mild and reversible side effects such as swelling, redness, and/or pain of injected site were observed in a few patients at dose level of 10 mg. There were no other toxic effects. In the latter 22 patients, immune parameters were measured weekly. After MY-1 treatment, enhanced PPD skin reaction and increased OKT4/OKT8 ratio in peripheral lymphocyte subsets were observed which were statistically significant especially at a dose level of 3 mg. The optimal dose and schedule for phase II clinical study were considered to be 3 mg s.c. 3 times a week. In addition, the methodology of the BRM phase I clinical study was discussed.
MY-1是从卡介苗中分离纯化得到的DNA组分，由水溶性和热变性核酸组成。临床前研究表明，MY-1对多种同基因肿瘤具有宿主介导的抗肿瘤活性，且在动物实验中显示出极低的毒性。鉴于这些结果提示MY-1可用作癌症治疗的生物反应调节剂（BRM），我们对患有各种恶性肿瘤的患者进行了I期临床研究。15例患者接受了0.25 - 20mg剂量的MY-1单次皮下注射治疗，随后22例患者在2周内每周3次皮下注射3 - 12.5mg的MY-1。在10mg剂量水平时，少数患者观察到注射部位出现肿胀、发红和/或疼痛等轻微且可逆的副作用。未观察到其他毒性作用。对后22例患者每周测量免疫参数。MY-1治疗后，观察到PPD皮肤反应增强，外周淋巴细胞亚群中OKT4/OKT8比值增加，尤其在3mg剂量水平时具有统计学意义。II期临床研究的最佳剂量和给药方案被认为是每周3次皮下注射3mg。此外，还讨论了BRM I期临床研究的方法。
