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DC vaccine & Anti-tumor

DC vaccine & Anti-tumor. “ 生命之树 ” 课题组： 孔琰　唐跃　田亚楠　　 　王超　王京　 王欠欠. The tumor induced immunity DC vaccine Induce in vitro & proliferation Classification DC vaccine The function of DC in anti-tumor Reinfuse of DC Our opinion. Inhibit formation of tumor vessel. Tolerance. Tumor Ag. DC.

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DC vaccine & Anti-tumor

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  1. DC vaccine & Anti-tumor “生命之树” 课题组： 孔琰　唐跃　田亚楠　　 　王超　王京　王欠欠

  2. The tumor induced immunity • DC vaccine • Induce in vitro & proliferation • Classification DC vaccine • The function of DC in anti-tumor • Reinfuse of DC • Our opinion

  3. Inhibit formation of tumor vessel Tolerance Tumor Ag DC T Migration proliferation CTL NO,TNF etc Cell apoptosis、lysis、CK The function of DC in anti-tumor Mechanism of DC in anti-tumor A B C

  4. Influence to DC from CKs produced by tumor VEGFC（血管内皮生长因子）——Depress the differentiation of pre-DC to mature DC IL-10——Inhibit the expression of co-stimulatory molecules TGF-ß——Inhibit the activation of specific CTL DC-SIGN

  5. DC vaccine Definition: the DC derive from peripheral blood mononuclear cells(PBMCs) are stimulated by peptide antigen,tumor lysates,whole-cell prepration RNA or DNA of tumor.And the reinfuse the DC into the patient as vaccine.

  6. GM-CSF / IL-4 CD14+DC GM-CSF / TNF-α CD34+ DC HOW TO GAIN DC ? DC vaccine Peripheral blood mononuclear cells are proper for clinical experiment.

  7. GM-CSF / IL-4 CD14+ DC GM-CSF / TNF-α CD34+ DC HOW TO GAIN DC ? DC vaccine Peripheral blood mononuclear cells are proper for clinical experiment.

  8. 2 Tumor cell lysate-sensitized DC Peptide-pulsed DC vaccine 1 3 DC-tumor cell hybrids 4 Ag pep loaded DC subcellular vaccine 5 Genetically modified DC vaccine Classification DC vaccine

  9. 1Peptide-pulsed DC vaccine The tumor peptide in HCC is mainly alpha-fetoprotein(AFP)

  10. Introduction AFP It has no affection to DC even at high concention. Glypican—3 HbsAg

  11. 1Peptide-pulsed DC vaccine Advantages Targeting, avoid unnecessary immune stimulation. higher concentration of tumor Ag stimulate the activation of T cell efficiently Disadvantages There is little confirmed; Specific recognization Little monoclonal tumor Ag

  12. Advantages： tumor cell Ag prepared by direct supersonic breakdown or repeated freezing&melting etc. is useful，no desire for Ag recognizing epitope Disadvantages: hard to supply large amount of fluid tissue； tumor lysate include normal self-Ag,which easily induce self-immune disease after immunization。 2Tumor cell lysate-sensitized DC

  13. 2Tumor cell lysate-sensitized DC Current Situation： Ladhams、Iwashita Ali Hayashi

  14. 3DC-tumor cell hybrids DC Tumor cell DC-Tumor hybrids ＋

  15. 3DC-tumor cell hybrids DC Tumor cell DC-Tumor hybrids ＋

  16. Hybrid cell Tumor cell Unrelated tumor cell Tumor cell

  17. Advantages Easily abtaned from biopsy、operation,HCC tissue specimen from；advanced skill to obtain pre-DC via cell culture；hybrid cell can present HCC Ag in the form of MHC pep complex；hybrid cells in vivo can stimulate to form lasing & steady Ag Disadvantages: Selection of hybrided cells 3DC-tumor cell hybrids

  18. 4Antigenic peptide loaded DC subcellular vaccine

  19. DC subcellular structure & other DC hybrids inhense expression of DC

  20. 5Genetically modified DC vaccine Antigen gene (HCC HBsAg AFP) Cytokine gene(GM-CSF IL-12) Chemotactic gene (lymphotactin Lpin)

  21. 5Genetically modified DC vaccine Advantages： AFP gene modefied DC vaccine can express completely endogenously & continuously reduce autoimmune diseases Disadvantages: The technology is not developed

  22. HOT SPOTS IL-18 & Survivin(存活素)

  23. Other methods to improve the effect of DC vaccine • NK cell& DC cell interaction • Heat shock protein（HSP） • Mannosalization of Ag

  24. Other methods to improve the effect of DC vaccine • NK cell& DC cell interaction • Heat shock protein（HSP） • Mannosalization of Ag

  25. Reinfuse of DC vaccine subcutaneous ? Lymph node venous

  26. WHAT DC CAN DO ?

  27. Produce selective T cell chemotactic factors Secrete CKs & cause damage Ag-loaded DC CD8+Tcell Migrate to lymph node &spleen Self or other APC secrete IL-12 CD4+Th0 Th1 IFN-γ TNF-α GM-CSF IL-3

  28. FORWARD Until now many cancers can be treated, such as: B cell lymphoma cancer Prostate cancer Malignant melanoma

  29. 曹雪涛(左)正在进行大肠癌DC疫苗研究

  30. Development and maturation of DC

  31. Difference between immature DC and mature DC

  32. Characteristics of DC： 1. the most potent APC 2.the only cell can active naïve T cell to elicit primary immune response. 3.play an significant role in anti-tumor

  33. NK cell& DC cell interaction DC attaches at the surface of NK cell and stimulates related receptors ,so these two cells can communicate in the form of neural synapse.

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