Indar A, Maxwell-Armstrong C A, Durrant L G, Carmichael J, Scholefield J H
Division of Surgery, Queens Medical Centre, Nottingham, UK.
J R Coll Surg Edinb. 2002 Apr;47(2):458-74.
Immunotherapy could have a role in the therapy of colorectal cancer as there is now convincing evidence that the immune system can specifically recognize and destroy malignant cells. The MAb 17-1A has been used in advanced and primary disease, along with newer agents such as anti-epidermal growth factor receptor (EGFR) antibody. Immunotherapy with autologous tumour cell vaccine, genetic modification of immunostimulatory cytokines, suicide genes and TAAs as discussed. The multiplicity of peptide and carbohydrate antigens which can be potential targets for immunotherapy are also discussed. These include MUC1, Thomsen-Friedenreich and Sialosyl-Tn antigens and HER2 / neu. Active specific immunotherapy with the anti-idiotypic antibodies CEAVac and 105AD7, along with DC vaccines, is being currently used in adjuvant clinical trials. 105AD7 has been shown to cause significantly greater apoptosis of tumour cells in colorectal cancer patients, while CEAVac generated T cell proliferative anti-CEA responses. Dendritic cells pulsed with tumour mRNA or TAAs currently are being assessed in clinical trials. The role of HSPs in the anti-tumour immune response is discussed. Non-specific immunotherapeutic agents used in clinical trials with chemotherapeutic regimens have not shown any definitive benefit. Tumour progression may occur as result of escape from the host anti-cancer immune response. Better understanding of mechanisms of tumour evasion could explain why immunotherapy trials in patients have not shown better results. These include down-regulation of immune responses by the tumour, altered expression of MHC and/or TAAs by tumour cells, altered expression of adhesion molecules by tumour and/or DCs and usurpation of the immune response to the advantage of the cancer.
免疫疗法在结直肠癌治疗中可能发挥作用，因为现在有令人信服的证据表明免疫系统能够特异性识别并摧毁恶性细胞。单克隆抗体17-1A已用于晚期和原发性疾病的治疗，同时还有一些新型药物，如抗表皮生长因子受体（EGFR）抗体。文中还讨论了自体肿瘤细胞疫苗免疫疗法、免疫刺激细胞因子的基因改造、自杀基因和肿瘤相关抗原。还讨论了可作为免疫疗法潜在靶点的多种肽和碳水化合物抗原，包括MUC1、汤姆森-弗里德赖希抗原和唾液酸化-Tn抗原以及HER2 / neu。抗独特型抗体CEAVac和105AD7以及树突状细胞疫苗的主动特异性免疫疗法目前正在辅助临床试验中使用。已证明105AD7能使结直肠癌患者的肿瘤细胞发生明显更多的凋亡，而CEAVac能产生T细胞增殖性抗CEA反应。目前正在临床试验中评估用肿瘤mRNA或肿瘤相关抗原脉冲处理的树突状细胞。文中讨论了热休克蛋白在抗肿瘤免疫反应中的作用。在与化疗方案联合进行的临床试验中使用的非特异性免疫治疗药物尚未显示出任何明确的益处。肿瘤进展可能是由于逃避宿主抗癌免疫反应所致。更好地理解肿瘤逃逸机制可以解释为什么在患者中进行的免疫疗法试验没有取得更好的结果。这些机制包括肿瘤对免疫反应的下调、肿瘤细胞对主要组织相容性复合体（MHC）和/或肿瘤相关抗原表达的改变、肿瘤和/或树突状细胞对黏附分子表达的改变以及利用免疫反应为癌症谋利。
