制片人 : 李晓颖 张媛媛 刘青 李芹 娄江华 田续江 刘波 张平 董铿 TumorImmunity

Tumor Immunity Tumor antigen is the new antigen produced by tumor cells. It can cause cell immune response and humoral immune response. Types: New protein,conformation-changed protein, hidden determinants,etc. New protein,conformation-changed protein, hidden determinants,etc.

NK cell NK cells play important roles in the NK cells play important roles in the early stage of immunity, are the first barrier. early stage of immunity, are the first barrier. Mechanism

NKG2D recptor Bind to MHC class I chain-related molecules A/B Bind to MHC class I chain-related molecules A/B MHC class I chain-related molecules A/B MHC class I chain-related molecules A/B express only on epicelial tumor cells express only on epicelial tumor cells Killing mechenism Perforin / Granzyme pathway Perforin / Granzyme pathway Fas FaslL interaction Fas FaslL interaction

Mφ 1. Activated Mφ bind with tumor cell and kill it directly by releasing lysozyme 2. Activated Mφ secrete TNF NO ect cytotoxic molecules to kill tumor indirectly 3. Process and present tumor cell and activate T cells by releasing cytokines ( IL-1,IL-12) 4. ADCC

DC High efficiency in presenting tumor Ag Promote the T cell to be active and multiply

T Cell CD4 +T cell : Secrete cytokines to activate CD8+ T cell Secrete cytokines to activate CD8+ T cell and macrophage CD8+ T cell: 1. recognize tumor specifically and kill tumor cells by releasing perforin, granzyme, FasL (bind to Fas on tumor cell 1. recognize tumor specifically and kill tumor cells by releasing perforin, granzyme, FasL (bind to Fas on tumor cell 2. secrete cytokines ( e.g. IFN-γ) and kill tumor cells indirectly 2. secrete cytokines ( e.g. IFN-γ) and kill tumor cells indirectly

肿瘤细胞破碎释放出肿瘤抗原 攻击肿瘤细胞 细胞因子 辅助信号 CD4+T 肿瘤抗原的加工、处理及有效果递 呈 CD4+T 细胞 肿瘤抗原特异性 CD4+T 细胞增殖 肿瘤抗原特异化的细胞毒性 T 细胞 （ CTL ） 特异性抗肿瘤细胞免疫应答过程

Humoral immunity Humoral immunity 1.ADCC 2.Opsonization 3.CDC (complement dependent cytotoxicyty) 4.Close some receptors on the tumor cells 5.Change the adhensin quality of tumor cell

Tumor Immunotherapy

Tumor immunotherapy Definition: Tumor immunotherapy is a kind of therapy which is to initiate or to enhance the immune function of our body, and then to prevent the tumor cells to diffuse or to kill the tumor cells. Tumor immunotherapy is a kind of therapy which is to initiate or to enhance the immune function of our body, and then to prevent the tumor cells to diffuse or to kill the tumor cells.

肿瘤复发 肿瘤消失 Oh, my god ! So magical ! 免疫治疗 肿瘤复发

Vaccine Immunotherapy Definition: Definition: The therapy that stimulate specifical anti-tumor immune response by injecting vaccine The therapy that stimulate specifical anti-tumor immune response by injecting vaccine

Tumor vaccine 1 Inactivated tumor vaccine 2 Subunit tumor vaccine 3 APC vaccine

Inactivated tumor vaccine Inactivated tumor vaccine

Subunit tumor vaccine

APC vaccine

Immunotherapy with monoantibody Definition: Definition: Use highly specific mAbs as carriers, coupled with cytotoxic kill molecules to kill tumour cells targetly. Use highly specific mAbs as carriers, coupled with cytotoxic kill molecules to kill tumour cells targetly. Chimeric mAb: Chimeric mAb: A human Fc attached to a mouse F(ab)2, reduce the risk of an immune response to the mAbs. A human Fc attached to a mouse F(ab)2, reduce the risk of an immune response to the mAbs.

Types: radioimmunotherapyAntibody-mediatedchemotherapyImmunotoxintherapy

Immunotoxintherapy Toxins coupled with mAbs can form immunotoxin and can kill the tumor cells specifically. Toxins coupled with mAbs can form immunotoxin and can kill the tumor cells specifically. Phytotoxin Phytotoxin RT( 蓖麻子毒素 ） Abrin （ 相思子毒素 ）, RT( 蓖麻子毒素 ） Abrin （ 相思子毒素 ）, Bacterotoxin Bacterotoxin DT （ 白喉毒素 ） PE （ 绿脓杆菌外毒素 ）. DT （ 白喉毒素 ） PE （ 绿脓杆菌外毒素 ）.

Genetic therapy Tumor cells may lose some genes or express abnormal genes. Transduce target gene to body and restore the function of tumor cells help them to express normal products.

Basic method Body cell gene therapy （ ex vivo ） target gene recombined with receptor cell target gene recombined with receptor cell Inject recombined receptor cell to patient body, so express the exogenous gene in patient Inject recombined receptor cell to patient body, so express the exogenous gene in patient Direct gene therapy Direct gene therapy Inject the exogenous gene to the patient body directly, and make it transcript and express. Inject the exogenous gene to the patient body directly, and make it transcript and express.

Adoptive immunotherapy Definition: Definition: Induce, activate or multiply the anti-tumor effective cells.Then transfuse the cells to patients to the cause anti-tumor function. Induce, activate or multiply the anti-tumor effective cells.Then transfuse the cells to patients to the cause anti-tumor function.

Adoptive immunotherapy LAK (lymphokine - activated natural killers) Lymphocytes from periphery blood,mainly NKT cell ★ Have no MHC restriction ★ It is non- specific immunotherapy ★ Kill the tumor cells which is not sensitive to ★ NK and CTL

Cytokine therapy The mechanism of cytokine therapy for tumor is that after being injected into body,the cytokine can regulate and increase the activity of immune cells,and have enhance anti-tumor effect. So far, IL-2,IFN-r,TNF-a and CSF have been used for tumor treatment. The mechanism of cytokine therapy for tumor is that after being injected into body,the cytokine can regulate and increase the activity of immune cells,and have enhance anti-tumor effect. So far, IL-2,IFN-r,TNF-a and CSF have been used for tumor treatment.

Interleukin-2 1. IL-2 is T cell growth factor, it can activate CD8+T cell 2. Induce and increase cytotoxic effection of the cytotoxic cells.(for example NK,CTL,). 3. It can also stimulate the activated T cell to produce IFN,IL-4~6 and CSF.

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