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L-BLP25:一种用于前列腺癌的靶向MUC1的肽疫苗疗法。

L-BLP25: a MUC1-targeted peptide vaccine therapy in prostate cancer.

作者信息

Sangha Randeep, North Scott

机构信息

Cross Cancer Institute, Department of Medical Oncology, 11560 University Avenue, Edmonton, Alberta, T6G 1H7, Canada.

出版信息

Expert Opin Biol Ther. 2007 Nov;7(11):1723-30. doi: 10.1517/14712598.7.11.1723.

Abstract

Renewed interest in cancer vaccine strategies has occurred with the identification of tumour-associated antigens and a further understanding of the immunoregulatory pathways involved in cancer development and progression. MUC1 is a mucinous glycoprotein that is overexpressed and aberrantly glycosylated in many human malignancies, including prostate cancer. BLP25 is a synthetic, liposomal cancer vaccine that targets the extracellular tandem repeat sequences of the MUC1 tumour-associated antigen. Preclinical L-BLP25 studies have shown the induction of a cell-mediated response and subsequent Phase I and II studies have established the vaccine dose, schedule and excellent safety profile. A Phase II study in advanced non-small cell lung cancer demonstrated a strong survival trend in favour of L-BLP25 in a subgroup of patients with locoregional stage IIIB disease. L-BLP25 also shows promise in prostate cancer. A pilot Phase II study in hormone naive patients with prostate-specific antigen failure after radical prostatectomy demonstrated a prolongation of prostate-specific antigen doubling time with little morbidity. These encouraging results suggest the potential of L-BLP25 in the management of cancer.

摘要

随着肿瘤相关抗原的发现以及对癌症发生和发展过程中免疫调节途径的进一步了解,人们对癌症疫苗策略重新产生了兴趣。MUC1是一种粘蛋白糖蛋白,在包括前列腺癌在内的许多人类恶性肿瘤中过度表达且糖基化异常。BLP25是一种合成脂质体癌症疫苗,靶向MUC1肿瘤相关抗原的细胞外串联重复序列。临床前L-BLP25研究显示可诱导细胞介导的反应,随后的I期和II期研究确定了疫苗剂量、给药方案以及良好的安全性。一项针对晚期非小细胞肺癌的II期研究表明,在局部晚期IIIB期疾病患者亚组中,L-BLP25具有显著的生存优势。L-BLP25在前列腺癌中也显示出前景。一项针对根治性前列腺切除术后前列腺特异性抗原失败的激素初治患者的II期试点研究表明,前列腺特异性抗原倍增时间延长,且不良反应轻微。这些令人鼓舞的结果表明L-BLP25在癌症治疗中具有潜力。

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