Section of Molecular Oncology and Immunotherapy, General Surgery, University Medical Center, Rostock D-18057, Germany.
World J Gastroenterol. 2018 Dec 28;24(48):5418-5432. doi: 10.3748/wjg.v24.i48.5418.
Therapeutic options for the treatment of colorectal cancer (CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hyper-mutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens (TAAs) and tumor-specific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptide-based vaccines achievable by adjuvants and immune-stimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens - in CRC almost exclusively neoantigens - which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immune-stimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.
治疗结直肠癌（CRC）的方法多种多样，但仍不尽如人意。最近，免疫检查点抑制治疗对患有高度突变肿瘤的 CRC 亚组患者的成功，表明免疫疗法在 CRC 的临床管理中具有持久作用。通过开发有效的个体化 CRC 疫苗接种策略，可以显著改善治疗效果。这篇迷你综述总结了目前关于两类靶点的知识：肿瘤相关抗原（TAA）和肿瘤特异性抗原。TAA 如癌胚抗原和黑色素瘤相关抗原存在于一部分患者中，并且为多种临床研究检测了不同 TAA 衍生肽疫苗的疗效。讨论了多种 TAA 的组合作为下一步以及个体化 TAA 肽疫苗的开发。通过佐剂和免疫刺激性化疗提高基于肽的疫苗的疗效。最后，我们总结了使用肿瘤特异性抗原的临床研究-在 CRC 中几乎完全是新抗原-这些研究结果显示出了有希望的结果；迄今为止，尚未报告严重的不良事件。通过个体化新抗原肽疫苗并将其与免疫刺激性化疗和免疫检查点抑制剂联合使用，有望为临床结果带来重大进展。鉴于这些数据和最新进展，真正个体化的基于新抗原的肽疫苗有望满足现代精准医学的要求，并将成为 CRC 常规临床管理的治疗支柱。
