微卫星不稳定结直肠癌相关肿瘤抗原的筛选、鉴定及其免疫治疗应用的研究

As the NCCN Clinical Practice Guidelines in colorectal cancer (version 2011) clearly points out that microsatellite instability (MSI) colorectal cancer patients cannot benefit from 5-Fu-based chemotherapy treatment, which makes these patients face a dilemma. Therefore, seeking new therapeutic methods for them is of great importance and becoming a hot-spot. Our preliminary study found that colorectal cancer patients with MSI are sensitive to thetreatment of dendritic cell vaccine, and that MSI-H highly expressed some certain important tumor antigen while MSS are not after further study. On this basis, further screening, identification, confirming the specificity and high immunogenicity of tumor-associated antigens would be conducted, and we would establish MAGE-A4-TCR-FasL bispecific T lymphocytes, and explore the outcome for MSI colorectal cancer. So exploring new treatment options for colorectal cancer with MSI is necessary and urgent, and our research would provide a new therapeutic approach and reference to treating colorectal cancer patients with MSI who do not benefit from chemotherapy of 5-Fu.

2011版的《NCCN结直肠癌临床实践指南》中明确指出，微卫星不稳定性（MSI）结直肠癌患者不能从5-Fu为基础的化疗受益。因此，探寻该类肿瘤新的治疗手段成为研究的热点。 本课题前期研究发现 MSI 结直肠癌患者对树突状细胞疫苗治疗敏感，进而对MSI-H/S 结直肠癌差异表达分子进行研究并初步发现其高表达某些重要的肿瘤抗原。在此基础上，本研究拟进一步筛选、鉴定、确证特异性和免疫原性较高的肿瘤相关抗原，并针对该抗原建立MAGE-A4特异性TCR-FasL双基因修饰T淋巴细胞系，并探讨其治疗MSI结直肠癌的疗效。通过本课题研究，探索和形成新的MSI结直肠癌治疗方案，为不能从5-Fu化疗方案中受益的MSI结直肠癌患者提供新的治疗途径和依据。