Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man
Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man
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DOI：
10.1073/pnas.96.10.5710
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发表时间：
1999-05-11
影响因子：
11.1
通讯作者：
Scher, HI
中科院分区：
文献类型：
--
作者：
Slovin, SF;Ragupathi, G;Scher, HI
已经合成了复杂的碳水化合物分子地球仪H六糖，将其与钥孔血蓝蛋白缀合，并与免疫佐剂QS-21一起施用，作为用于在初级治疗（如放射或手术）后复发的前列腺癌患者的疫苗。地球仪H是存在于前列腺癌细胞上的几种候选抗原之一，其可以用作免疫识别和治疗策略的靶标。该疫苗在26周内皮下接种5次，已被证明是安全的，并能诱导特异性高滴度IgM抗体抗地球仪H。其免疫原性在具有广泛分期和肿瘤负荷的前列腺癌患者中得到证实。对几名有疾病复发证据的患者进行的观察仅限于升高的生化标志物前列腺特异性抗原（PSA），表明在完成疫苗治疗后3个月内可能出现治疗效果。这种效应表现为治疗后PSA浓度对数与时间曲线的斜率与治疗前值相比下降。5例患者在没有任何影像学疾病证据的情况下持续具有稳定的PSA斜率曲线超过2年，使用PSA斜率曲线评估生物疗法（如疫苗）的早期治疗效果的概念有待于II期和III期试验的进一步验证。在前列腺癌中使用多种鲜为人知的候选糖蛋白和碳水化合物抗原作为开发治疗具有最小肿瘤负荷的患者中的复发性前列腺癌的多价疫苗的焦点。
The complex carbohydrate molecule globe H hexasaccharide has been synthesized, conjugated to keyhole limpet hemocyanin, and administered with the immunologic adjuvant QS-21 as a vaccine for patients with prostate cancer who have relapsed after primary therapies such as radiation or surgery, Globe H is one of several candidate antigens present on prostate cancer cells that can serve as targets for immune recognition and treatment strategies. The vaccine, given as five subcutaneous vaccinations over 26 weeks, has been shown to be safe and capable of inducing specific high-titer IgM antibodies against globe H. Its immunogenicity was confirmed in prostate cancer patients with a broad range of stages and tumor burdens. Observations of several patients who had evidence of disease relapse restricted to a rising biochemical marker, prostate-specific antigen (PSA), indicated that a treatment effect could occur within 3 months after completion of the vaccine therapy. This effect was manifested as a decline of the slope of the log of PSA concentration vs, time plot after treatment compared with values before treatment. Five patients continue to have stable PSA slope profiles in the absence of any radiographic evidence of disease for more than 2 years, The concept of using PSA slope profiles in assessing early treatment effects in biological therapies such as vaccines awaits further validation in phase II and III trials. The use of a variety of lesser known candidate glycoprotein and carbohydrate antigens in prostate cancer serves as a focus for the development of a multivalent vaccine of the treatment of relapsed prostate cancer in patients with minimal tumor burden.