CLINICAL TRIALS WITH A POLYVALENT BREAST CANCER VACCINE

糖类抗原是在大肠杆菌中表达最丰富的抗原。 大多数癌症的细胞表面和一些已经被证明， 作为主动和被动具体的有效目标， 临床试验中的免疫疗法。既往活检研究 标本显示，大多数乳腺癌细胞表达 表面活性剂的主要成分有：T-F、sTn、刘易斯-Le 和Globo H碳水化合物抗原，以及肽抗原MUCI。 结合疫苗已被证明是最有效的方法 增强针对碳水化合物和肽的抗体应答 抗原在我们的经验。 匙孔血蓝蛋白（KLH）具有 是最有效的载体分子，皂苷级分QS-21 最有效的免疫佐剂。我们已完成应计费用 在患有以下疾病的患者中使用MUCl-KLH加QS 21疫苗的试点试验 最近开始了一项sTn（c）-KLH的试点试验， 在同一个患者群体中接种疫苗。sTn（c）试验基于 我们最近观察到，单克隆抗体识别的抗原 抗体B72.3是以簇构象表达的sTn [sTn（c）]。 已合成TF、Le和Globo H抗原，与 KLH和相关免疫原性已在 老鼠. 在本提案中，我们试图测试这些疫苗的免疫原性。 在乳腺癌患者中进行的I/II期研究中的单抗原疫苗， 构建一致的免疫原性多价疫苗， 测试它的免疫原性和毒性一项大型多中心 下半年将启动随机III期临床试验 2期或3期乳腺癌患者的第三年， 辅助化疗后无可检测的疾病，但在高 发展为复发性疾病的风险。

Carbohydrate antigens are the most abundantly expressed antigens on the cell surface of most cancers and several have been shown to function as effective targets for active and passive specific immunotherapy in clinical trials. Previous studies of biopsy specimens have shown that most breast Cancers express at the cell surface the Thomsen-Friedenreich (TF), sialyl Tn (sTn), Lewis- (Le) and Globo H carbohydrate antigens, and the peptide antigen MUCI. Conjugate Vaccines have proven the most effective approach to augmenting the antibody response against carbohydrate and peptide antigens in our experience. Keyhole limpet hemocyanin (KLH) has been the most potent carrier molecule and the saponin fraction QS-2l the most potent immunological adjuvant. We have completed accrual to a pilot trial with a MUCl-KLH plus QS21 vaccine in patients with breast cancer and recently initiated a pilot trial with an sTn(c )-KLH vaccine in this same patient population. The sTn(c) trial is based on our recent observation that the antigen recognized by monoclonal antibody B72.3 is sTn expressed in a cluster conformation [sTn(c)]. TF, Le and Globo H antigens have been synthesized, conjugated to KLH, and relevant immunogenicity has been confirmed in the mouse. In this proposal, we seek to test the immunogenicity of these single antigen vaccines in Phase I/II studies in breast cancer patients, to construct a consistently immunogenic polyvalent vaccine, and to test this for immunogenicity and toxicity. A large multicenter randomized Phase III clinical trial will be initiated in the second half of year three in patients with Stage 2 or 3 breast Cancer who are free of detectable disease after adjuvant chemotherapy but are at high risk of developing recurrent disease.