Dc vaccine anti tumor
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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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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


Dc vaccine anti tumor

  • 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


The function of dc in anti tumor

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


Influence to dc from cks produced by tumor

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


Dc vaccine

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.


How to gain dc

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.


How to gain dc1

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.


Classification dc vaccine

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


1 peptide pulsed dc vaccine

1Peptide-pulsed DC vaccine

The tumor peptide in HCC is mainly alpha-fetoprotein(AFP)


Introduction

Introduction

AFP It has no affection to DC even at high concention.

Glypican—3

HbsAg


1 peptide pulsed dc vaccine1

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


2 tumor cell lysate sensitized dc

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


2 tumor cell lysate sensitized dc1

2Tumor cell lysate-sensitized DC

Current Situation:

Ladhams、Iwashita

Ali

Hayashi


Dc vaccine anti tumor

3DC-tumor cell hybrids

DC

Tumor cell

DC-Tumor hybrids


Dc vaccine anti tumor

3DC-tumor cell hybrids

DC

Tumor cell

DC-Tumor hybrids


Dc vaccine anti tumor

Hybrid cell

Tumor cell

Unrelated tumor cell

Tumor cell


Dc vaccine anti tumor

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


4 antigenic peptide loaded dc subcellular vaccine

4Antigenic peptide loaded DC subcellular vaccine


Dc vaccine anti tumor

DC subcellular structure & other DC hybrids inhense expression of DC


5 genetically modified dc vaccine

5Genetically modified DC vaccine

Antigen gene (HCC HBsAg AFP)

Cytokine gene(GM-CSF IL-12)

Chemotactic gene (lymphotactin Lpin)


5 genetically modified dc vaccine1

5Genetically modified DC vaccine

Advantages:

AFP gene modefied DC vaccine can express

completely endogenously & continuously

reduce autoimmune diseases

Disadvantages:

The technology is not developed


Hot spots

HOT SPOTS

IL-18 & Survivin(存活素)


Other methods to improve the effect of dc vaccine

Other methods to improve the effect of DC vaccine

  • NK cell& DC cell interaction

  • Heat shock protein(HSP)

  • Mannosalization of Ag


Other methods to improve the effect of dc vaccine1

Other methods to improve the effect of DC vaccine

  • NK cell& DC cell interaction

  • Heat shock protein(HSP)

  • Mannosalization of Ag


Reinfuse of dc vaccine

Reinfuse of DC vaccine

subcutaneous

?

Lymph node

venous


Dc vaccine anti tumor

WHAT DC CAN DO ?


Dc vaccine anti tumor

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


Forward

FORWARD

Until now many cancers can be treated,

such as:

B cell lymphoma cancer

Prostate cancer

Malignant melanoma


Dc vaccine anti tumor

曹雪涛(左)正在进行大肠癌DC疫苗研究


Dc vaccine anti tumor

Development and maturation of DC


Difference between immature dc and mature dc

Difference between immature DC and mature DC


Dc vaccine anti tumor

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


Nk cell dc cell interaction

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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