Zheng Lei, Edil Barish H, Soares Kevin C, El-Shami Khaled, Uram Jennifer N, Judkins Carol, Zhang Zhe, Onners Beth, Laheru Daniel, Pardoll Drew, Jaffee Elizabeth M, Schulick Richard D
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ann Surg Oncol. 2014 Nov;21(12):3931-7. doi: 10.1245/s10434-014-3844-x. Epub 2014 Jun 19.
Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic colorectal carcinoma remains poor. Immunotherapy is a potentially effective therapeutic approach to the treatment of colorectal carcinoma. Preclinical studies have supported the antitumor activity of immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine.
A novel colorectal cancer vaccine composed of irradiated, allogeneic human colon cancer cells and GM-CSF-producing bystander cells was developed and tested in combination with a single intravenous low dose of cyclophosphamide in a phase 1 study of patients with metastatic colorectal cancer.
A total of nine patients were enrolled onto and treated in this study. Six patients had a history of colorectal adenocarcinoma hepatic metastases and underwent curative metastasectomy, while three other patients had unresectable stage IV disease. This study demonstrates the safety and feasibility of this vaccine administered in patients with metastatic colorectal cancer. At last follow-up, the six patients who underwent curative metastasectomy survived longer than 36 months, and four of these six patients were without disease recurrence. Immunologic correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances the production of anti-MUC1 antibodies.
This vaccine is feasible and safe. Future investigation of the efficacy and antitumor immunity of this vaccine is warranted.
尽管近期在早期检测方面取得了进展,化疗也有所改善,但转移性结直肠癌患者的5年生存率仍然很低。免疫疗法是治疗结直肠癌的一种潜在有效治疗方法。临床前研究支持用产生粒细胞-巨噬细胞集落刺激因子(GM-CSF)的鼠结肠肿瘤细胞疫苗进行免疫的抗肿瘤活性。
开发了一种新型结直肠癌疫苗,其由经辐照的同种异体人结肠癌细胞和产生GM-CSF的旁观者细胞组成,并在转移性结直肠癌患者的1期研究中与单次静脉内低剂量环磷酰胺联合进行测试。
本研究共纳入9例患者并进行治疗。6例患者有结直肠癌肝转移病史并接受了根治性转移灶切除术,另外3例患者患有不可切除的IV期疾病。本研究证明了这种疫苗在转移性结直肠癌患者中给药的安全性和可行性。在最后一次随访时,接受根治性转移灶切除术的6例患者存活时间超过36个月,这6例患者中有4例无疾病复发。免疫相关结果表明,产生GM-CSF的结肠癌疫苗可增强抗MUC1抗体的产生。
这种疫苗是可行且安全的。有必要对该疫苗的疗效和抗肿瘤免疫进行进一步研究。