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肿瘤免疫逃逸和生物调变分子机制的研究

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肿瘤免疫逃逸和生物调变分子机制的研究 - PowerPoint PPT Presentation


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国家自然科学奖汇报资料. 肿瘤免疫逃逸和生物调变分子机制的研究. 郭亚军(第二军医大学). 肿瘤杀伤. 肿瘤发生发展转移. 肿瘤识别. 免疫调节. 肿瘤排斥. 研究背景. 肿瘤抗原 —— 性质与提呈 机体反应 —— 识别与排斥 免疫逃逸与转移 —— 粘附受体 免疫调节 —— 共刺激分子. 发现点之一. 肿瘤细胞存在肿瘤特异性 抗原 肿瘤特异性抗原的隐蔽是 由于其提呈功能的系统性缺失 肿瘤抗原提呈系统修复和重建的新理论. 细胞融合肿瘤抗原提呈模型. APC. 共刺激分子. MHC. 细胞融合. +. Tumor Vaccine.

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slide2

肿瘤杀伤

肿瘤发生发展转移

肿瘤识别

免疫调节

肿瘤排斥

slide3
研究背景
  • 肿瘤抗原——性质与提呈
  • 机体反应——识别与排斥
  • 免疫逃逸与转移——粘附受体
  • 免疫调节——共刺激分子
slide4
发现点之一
  • 肿瘤细胞存在肿瘤特异性抗原
  • 肿瘤特异性抗原的隐蔽是由于其提呈功能的系统性缺失
  • 肿瘤抗原提呈系统修复和重建的新理论
slide5

细胞融合肿瘤抗原提呈模型

APC

共刺激分子

MHC

细胞融合

+

Tumor Vaccine

Tumor cell

cytokines

slide6

MHC class I

molecule

Tumor antigen

CD8+

T cell

T-cell receptor

Cytotoxic

T cell

APC

Co-stimulatory

molecule

Fusion

Tumor

cell

Receptor for

co-stimulatory

molecule

CD8+

T cell

CD4+

T cell

MHC class II

molecule

cytokines

slide8

tumor

T cell

tumor

T cell

MHC-I

TCR

MHC-I

TCR

CD8

CD8

MHC-II

MHC-II

TCR

TCR

CD4

CD4

41BBL

41BB

41BBL

41BB

B7

CD28

B7

CD28

ICAM-1

LFA-1

ICAM-1

LFA-1

bs-mAb

Bridge tumor cell to T cells by bi-specific mAb greatly facilitate the interaction of adhesion molecular that costimulate T cell activation

slide9

MHC-I

The First Step

Treatment of tumor cell in vitro with combination of cytokines to enhance tumor antigen proccessing and expression of adhesion molecule

B7

MHC-II

Tumor Cells

ICAM-1

Tumor Cells

Cytokines Treating

slide10

Tumor Cells

Tumor Cells

+

The Second Step

Bi-specific mAb coating on the cytokine treated tumor cell surface

slide11

Nature Medicine, 3(4) :451- 455

PNAS, 101(14): 4990- 4995

Cancer Gene Therapy, 12: 769- 777

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