CLINICAL TRIALS WITH ACTIVE AND PASSIVE IMMUNOTHERAPY AGAINST OVARIAN CANCER

在本项目中，两种基于抗体的卵巢癌治疗方法 癌症是有计划的。一种是基于结合物的主动免疫治疗 一种是疫苗，另一种是用放射性标记的被动疗法 抗体。大多数卵巢癌在细胞表面GM2表达 神经节苷脂、Thomsen-Friedenreich(Tf)、唾液酸甘油酯 构象(STN(C))、Lewis(Le/y)和Globo H糖类抗原， 蛋白抗原MUC-1和KSA，以及MX35抗原。对于定义明确的 碳水化合物和多肽抗原，结合疫苗已经被证明是最 增强抗体反应的有效方法。锁孔帽状物 血蓝蛋白(KLH)是最主要的载体分子，也是皂素 组分QS-21是最具免疫力的佐剂。我们现在有了KLH共轭 加上QS-21疫苗，能够持续诱导抗体应答 抗GM2、STN(C)、Globo H和MUC-1的患者。与Le/y的试验是 目前正在进行卵巢癌患者的试验和KSA和TF(C)的试验 结合疫苗计划在1998年上半年进行。首字母 项目III的目标是构建始终如一的免疫原性 卵巢癌多价疫苗，以测试其免疫原性 和毒性，并比较全身和腹膜抗体效价 接种后通过皮下或腹膜途径接种。A阶段 这种多价疫苗的临床试验将于#年末启动。 转移性卵巢癌患者的第二年 辅助化疗后大体可检测到疾病，二次检查 手术，以及顺铂和依托泊苷的腹腔注射。 放射性标记抗体131/I MX35 F(ab‘)2已被证实可定位 对卵巢癌腹膜转移的抑制作用 治疗试验正在进行中；初步剂量测定结果表明 巨大的治疗潜力。有明显疾病(&lt；1厘米)的患者 第二次/看手术)将在一秒内用131/I-MX35 F(AB‘)2治疗 第二阶段试验。

In this project, two antibody-based approaches to the therapy of ovarian cancer are planned. One is based on active immunotherapy with conjugate vaccines and the other utilizes passive therapy with a radiolabeled antibody. Most ovarian cancers express at the cell surface GM2 ganglioside, the Thomsen-Friedenreich (TF), sialyl TN in cluster conformation (STN(C)), Lewis (Le/y) and Globo H carbohydrate antigens, the protein antigens MUC-1 and KSA, and the MX35 antigen. For well-defined carbohydrate and peptide antigens, conjugate vaccines have proven the most effective approach to augmenting the antibody response. Keyhole limpet hemocyanin (KLH) has been the most carrier molecule and the saponin fraction QS-21 the most immunological adjuvant. We now have KLH conjugate plus QS-21 vaccines capable of consistently inducing antibody responses in patients against GM2, sTn(C), Globo H, and MUC-1. A trial with Le/y is currently ongoing in ovarian cancer patients and trials with KSA and TF(C) conjugate vaccines are planned for the first half of 1998. The initial goals of Project III are to construct a consistently immunogenic polyvalent vaccine against ovarian cancer, to test this for immunogenicity and toxicity, and to compare systemic and intraperitoneal antibody titers after vaccination by the subcutaneous or intraperitoneal routes. A Phase II clinical trials with this polyvalent vaccine will be initiated late in the second year in patients with metastatic ovarian cancer who are free of grossly detectable disease after adjuvant chemotherapy, second-look surgery, and administration of intraperitoneal cisplatin and etoposide. The radio-labeled antibody 131/I MX35 F(ab')2 has been shown to localize to ovarian cancer peritoneal metastases when administered IP.A Phase I therapeutic trial is in progress; initial dosimetry results suggest significant therapeutic potential. Patients with visible disease (<1cm at second/look surgery) will be treated with 131/I-MX35 F(AB')2 in a second Phase II trial.