Tumour antigens recognized by

cancer immunotherapy  

Identification of mouse antigens  

Initial controversy about the existence of tumour rejection antigens.  

子主题

Molecular identification of antigens recognized by T lymphocytes on mouse tumours  

timeline

Identification of human antigens  

Genetic approach.  

Biochemical approach. 

Reverse immunology.  

Human antigens: classes  

Antigens of high tumoural specificity  

viral antigens：病毒性致癌：宫颈癌、肝癌、鼻咽癌、白血病

Mutated genes：the other half being encoded by cancer-germline genes 肺癌（吸烟）、黑素瘤（紫外线）、直肠癌（DNA修复错误）

cell cycle regulation CDK4，影响了抑癌基因INK4A

CASP8

chromosomaltranslocations.

突变型抗原未用于治疗

antigens that are encoded by cancer-germlinegenes这些基因的表达与启动子脱甲基化有关（正常组织内不表达？） 5ʹ-aza-2ʹ-deoxycytidine用于vaccination or adoptive T cell transfer.

Antigens of low tumoural specificity. 

differentiation antigens

melanocyte differentiation antigen:Melan-A

The prostate expresses differentiationprotein

antigens derived from proteins that are overexpressed in tumours

Quantitativereverse transcription PCR 和Immunohistochemical analysis 

breast cancer：The oncogene and growth factor receptorERBB2

leukaemic cells：WT1

adenocarcinomas ：MUC1

Tumour specificity and potential side effectsof immunotherapy.  

natural tolerance（AIRE）：MAGE genes，P1A-encoding gene Trap1a（当下研究结论的误区）

vaccine（少数有问题）VS CTLA4

We nowbelieve that the usual procedures that involvethe in vitro stimulation of T cells of cancerpatients with the autologous tumour cell linedo not activate naive cells but only activatememory T cells that result from a previousspontaneous response against the tumour.

reverse immunology:a substantial riskof adverse side effects

MAGEA3 protein vaccination 无危险报道

原因：crossreacts with a cardiac protein；低肿瘤特异性抗原增加

Adoptive transfer of expanded populations of tumour-infiltrating lymphocytesfrom patients with melanoma

uveitis

Perspectives for immunotherapy  

Antibodies against CTLA4：a releaseof the peripheral tolerance

过继性T细胞移植最有前景：CTL和无修饰的T细胞受体

疫苗有点成就，5%-10%

错误的看法，真实是刺激记忆T细胞

non-toxic inhibitors of immunosuppression