肿瘤免疫研究生教学课件.ppt

Cancer regression in two patients. (A) Computed tomography (CT) images of liver metastasis in patient 4 taken at pretreatment, 1 month, and 10 months after treatment with TCR-engineered T cells. (B) Size of liver and axillary tumors and tempo of regression of tumor sites in patient 4. Day 0, beginning of treatment. L Axill LN, left axillary lymph node. (C) CT images of hilar lymph node metastasis in patient 14; pretreatment, day 0, and 2 months and 12 months after treatment. The white arrow indicates the mass in the lung hilum. (D) Size of tumor and tempo of regression in patient 14. (E) Quantitation of gene-marked cells in the PBMCs of patients 4 and 14 was determined by real-time quantitative PCR. Pt, patient. Day of infusion (Inf.) indicated by arrow. (F) The percentage of CD8+/Vβ12+ cells in the intermediate gate (13) in the circulation of patients 4 and 14. * Antibodies are highly specific and can bind and affect disease-specific targets, causing fewer toxic side-effects than traditional cytotoxic chemotherapies. Moreover, antibodies are effective through a variety of mechanisms to kill cancer cells that give hope for improvement of survival in many cancers and are the focus of much research in oncology. * Two challenges were one is the immunogencity of mouse’s monoclonal antibody, the human anti-mouse antibody response. the second is lack of adequate targets on tumor cells, it is the antigenic heterogeneity of cancer cells. * And up to new, seven antibodies based therapeutic for cancer treatment in market. * 免疫检验点阻断剂 肿瘤疫苗 过继免疫细胞疗法 其他新型免疫疗法 定义和 类型 免疫检验点可以调节免疫反应强度，避免正常组织的损伤，往往被肿瘤细胞利用来逃避免疫细胞的攻击。免疫检验点阻断剂可以解除免疫检验点的抑制状态。 包括：CTLA4阻断剂、PD-1阻断剂、PD-L1阻断剂 给患者体内导入肿瘤抗原来激活人体的免疫细胞，克服肿瘤产物所引起的免疫抑制状态，促进树突状细胞的抗原提呈功能来消灭肿。 包括：肿瘤细胞疫苗、肿瘤抗原疫苗、肿瘤DNA疫苗、树突状细胞疫苗、细菌疫 从肿瘤患者中分离免疫活性细胞，在体外进行扩增和功能鉴定，然后向患者转输，从而直接杀伤肿瘤或激发机体的免疫应答杀伤肿瘤细胞。 包括：淋巴因子激活的杀伤细胞疗法、细胞因子介导的杀伤细胞疗法、肿瘤浸润性淋巴细胞治疗（TIL）、T细胞受体基因治疗（TCR基因治疗）、嵌合抗原受体治疗（CAR-T细胞治疗） CD19药物（双特异性T细胞衔接系统） 联合免疫疗法 药品上市进展 2011年，FDA批准了第一种免疫检验点阻断剂。 Ipilimumab（CTLA4