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

“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

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

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

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.


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.


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.


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


1Peptide-pulsed DC vaccine

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


Introduction

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

Glypican—3

HbsAg


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


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


2Tumor cell lysate-sensitized DC

Current Situation:

Ladhams、Iwashita

Ali

Hayashi


3DC-tumor cell hybrids

DC

Tumor cell

DC-Tumor hybrids


3DC-tumor cell hybrids

DC

Tumor cell

DC-Tumor hybrids


Hybrid cell

Tumor cell

Unrelated tumor cell

Tumor cell


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


4Antigenic peptide loaded DC subcellular vaccine


DC subcellular structure & other DC hybrids inhense expression of DC


5Genetically modified DC vaccine

Antigen gene (HCC HBsAg AFP)

Cytokine gene(GM-CSF IL-12)

Chemotactic gene (lymphotactin Lpin)


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

IL-18 & Survivin(存活素)


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 vaccine

  • NK cell& DC cell interaction

  • Heat shock protein(HSP)

  • Mannosalization of Ag


Reinfuse of DC vaccine

subcutaneous

?

Lymph node

venous


WHAT DC CAN DO ?


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

Until now many cancers can be treated,

such as:

B cell lymphoma cancer

Prostate cancer

Malignant melanoma


曹雪涛(左)正在进行大肠癌DC疫苗研究


Development and maturation of DC


Difference between immature DC and mature DC


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

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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