Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1020 Locust Street, JAH 348A, Philadelphia, PA 19107, USA.
Immunol Res. 2011 Dec;51(2-3):161-9. doi: 10.1007/s12026-011-8253-7.
For the last decade, we have focused on guanylyl cyclase C (GUCY2C) as a potentially ideal target antigen for colorectal cancer immunotherapy. GUCY2C is expressed only in intestinal epithelial cells and by nearly 100% of colorectal cancers. We have developed and tested a recombinant adenoviral vector possessing GUCY2C (Ad5-GUCY2C) as a candidate vaccine for colorectal cancer patients. Murine studies have revealed that this vaccine is safe and effective against GUCY2C-expressing targets, and Ad5-GUCY2C is poised for phase I clinical testing in colorectal cancer patients with minimal residual disease. Moreover, we are developing second-generation GUCY2C-targeted therapeutics, including the use of chimeric antigen receptor (CAR)-expressing T cells, for treatment of patients with advanced colorectal cancer for whom Ad5-GUCY2C immunization is not appropriate. Thus, a family of GUCY2C-targeted immunotherapeutics may bridge the gap in effective treatments for the 500,000 patients worldwide who die annually from colorectal cancer.
在过去的十年中，我们一直专注于鸟苷酸环化酶 C（GUCY2C）作为结直肠癌免疫治疗的潜在理想靶抗原。GUCY2C 仅在肠上皮细胞中表达，几乎 100%的结直肠癌都表达。我们已经开发并测试了一种携带 GUCY2C 的重组腺病毒载体（Ad5-GUCY2C），作为结直肠癌患者的候选疫苗。 小鼠研究表明，这种疫苗对表达 GUCY2C 的靶标是安全有效的，Ad5-GUCY2C 准备在结直肠癌患者中进行 I 期临床试验，这些患者的残留疾病较少。 此外，我们正在开发第二代 GUCY2C 靶向治疗药物，包括使用嵌合抗原受体（CAR）表达的 T 细胞，用于治疗不适合 Ad5-GUCY2C 免疫接种的晚期结直肠癌患者。 因此，一系列 GUCY2C 靶向免疫疗法可能会填补全球每年有 50 万名死于结直肠癌的患者缺乏有效治疗方法的空白。
