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 hyp...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 hypermutated 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 tumorspecific 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 peptidebased vaccines achievable by adjuvants and immunestimulatory 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 immunestimulatory 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.展开更多
个性化肿瘤(癌症)疫苗(personalized cancer vaccines,PCVs)包括新抗原癌症(肿瘤)疫苗(neoantigen cancer vaccines,NCVs)和肿瘤裂解物疫苗(tumor lysate vaccines,TLVs)。NCVs以新表位为抗原。新表位是新抗原中可以激活肿瘤特异性T细...个性化肿瘤(癌症)疫苗(personalized cancer vaccines,PCVs)包括新抗原癌症(肿瘤)疫苗(neoantigen cancer vaccines,NCVs)和肿瘤裂解物疫苗(tumor lysate vaccines,TLVs)。NCVs以新表位为抗原。新表位是新抗原中可以激活肿瘤特异性T细胞的免疫活性肽。新抗原是根据肿瘤细胞全基因组测序数据确定的肿瘤细胞特有的突变蛋白。TLVs以肿瘤患者的肿瘤裂解物为抗原。PCVs能激活肿瘤特异性CD4+T细胞和CD8+T细胞,这些T细胞能在肿瘤患者体内抑制、杀伤肿瘤细胞,因而延长肿瘤患者的生存期。为了提高疫苗效力,PCVs必须和佐剂组成一定的剂型。可用于PCVs的佐剂有运载体、纳米颗粒、乳化剂、模式识别受体激动剂、免疫卡点抑制剂和能改变免疫抑制肿瘤微环境的制剂等。展开更多
基金Supported by Ministerium für Wirtschaft,Arbeit und Gesundheit Mecklenburg-Vorpommern,No.TBI-V-1-241-VBW-084
文摘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 hypermutated 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 tumorspecific 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 peptidebased vaccines achievable by adjuvants and immunestimulatory 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 immunestimulatory 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.
文摘个性化肿瘤(癌症)疫苗(personalized cancer vaccines,PCVs)包括新抗原癌症(肿瘤)疫苗(neoantigen cancer vaccines,NCVs)和肿瘤裂解物疫苗(tumor lysate vaccines,TLVs)。NCVs以新表位为抗原。新表位是新抗原中可以激活肿瘤特异性T细胞的免疫活性肽。新抗原是根据肿瘤细胞全基因组测序数据确定的肿瘤细胞特有的突变蛋白。TLVs以肿瘤患者的肿瘤裂解物为抗原。PCVs能激活肿瘤特异性CD4+T细胞和CD8+T细胞,这些T细胞能在肿瘤患者体内抑制、杀伤肿瘤细胞,因而延长肿瘤患者的生存期。为了提高疫苗效力,PCVs必须和佐剂组成一定的剂型。可用于PCVs的佐剂有运载体、纳米颗粒、乳化剂、模式识别受体激动剂、免疫卡点抑制剂和能改变免疫抑制肿瘤微环境的制剂等。
