CLINICAL TRIALS WITH ACTIVE AND PASSIVE IMMUNOTHERAPY AGAINST OVARIAN CANCER

在这个项目中，两种基于抗体的方法来治疗卵巢癌， 癌症是有计划的。一种是基于偶联物的主动免疫疗法， 疫苗，另一种利用放射性标记的被动疗法。 抗体的大多数卵巢癌在细胞表面表达GM 2 神经节苷脂、神经节苷脂（TF）、唾液酸TN簇 构象（C）、刘易斯（Le/y）和Globo H碳水化合物抗原， 蛋白抗原MUC-1和KSA，以及MX35抗原。对于定义明确的 碳水化合物和肽抗原，结合疫苗已被证明是最 增强抗体反应的有效方法。匙孔 血蓝蛋白（KLH）是最主要的载体分子， 组分QS-21的免疫佐剂作用最强。我们现在有KLH共轭 加上QS-21疫苗能够持续诱导抗体应答， 抗GM 2、sTn（C）、Globo H和MUC-1的患者。与Le/y的试验是 目前正在卵巢癌患者中进行KSA和TF试验（C） 计划在1998年上半年生产结合疫苗。初始 项目III的目标是构建一个一致的免疫原性 卵巢癌多价疫苗的免疫原性 和毒性，并比较全身和腹膜内抗体滴度 通过皮下或腹膜内途径接种后。相位 这种多价疫苗的II期临床试验将于2009年晚些时候启动。 第二年，转移性卵巢癌患者没有 辅助化疗后肉眼可检测的疾病，二次检查 手术和腹膜内施用顺铂和依托泊苷。 放射性标记的抗体131/IMX 35 F（ab '）2已显示定位于 腹膜内给药时卵巢癌腹膜转移的I期 治疗试验正在进行中;初步剂量测定结果表明 显著的治疗潜力。可见病变的患者（<1cm， 第二次/外观手术）将在第二次手术中用131/I-MX35 F（AB '）2治疗 二期试验。

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.