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Tumor immunotherapy. 张沛. 张书铭. 张黎明. 赵宸. 赵世刚. Tumour Immunotherapy: questions. Can immune stimulators combat cancer? Which forms of immunotherapy can be used? Is vaccination effective against established tumours? Can anti-tumour responses be generated in vitro ?

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Tumor immunotherapy
Tumor immunotherapy

张沛

张书铭

张黎明

赵宸

赵世刚


Tumour immunotherapy questions
Tumour Immunotherapy: questions

  • Can immune stimulators combat cancer?

  • Which forms of immunotherapy can be used?

  • Is vaccination effective against established tumours?

  • Can anti-tumour responses be generated in vitro?

  • Can in vitro responses translate into in vivo effects?

  • What barriers are there to development of effective IT?

  • ……???



N o 1 passive immunotherapy

Apoptosis induction

Complement-mediated cytotoxicity

ADCC

Conjugated to toxin / isotope

NK

N.o 1 ‘Passive’ immunotherapy

  • Adminstration of monoclonal antibodies which target either tumour-specific or over-expressed antigens.

  • Kill tumour cells in a variety of ways:


STRESSES

N.o 2Heat Shock Proteins for Therapy

HSPs protect the delicate functions of the cell.


COOH

NH4

Heat Shock Proteins(HSP70)

ATPase

peptide-binding domain

tumour peptide sequence


CTL

Hsp70 or gp96 / peptide complex

NK

tumour peptides presented to CTL / NK cells via HLA Class I

TAP system

Transporter Associated with Peptide processing

How is the anti-tumour effect produced?

CD91

endocytosis

receptor

APC


Vaccination using hsp complexes
Vaccination using HSP complexes

Peripheral blood from CML patient

Isolate HSP complexes from tumour cells

APC

Load APCwith HSP complexes in vitro

Co-culture with patient T cells and expand effectors for infusion into patient

Immunize patient directly with tumour antigen-primed APC


COOH

NH4

Heat Shock Proteins(HSP70)

ATPase

peptide-binding domain

tumour peptide sequence


Survival rates in a model of lymphoma

Immunized with PBS ()

40 µg HSP70 from liver ()

20 µg HSP70 A20 cells ()

40 µg HSP70 A20 cells ()


N.o 3 Dendritic cell therapy

  • Dendritic cells are key components of the adaptive immune response ,can activatenaive T cell

  • APC function with ability to direct IR (activation/tolerance)

  • Present in peripheral blood as circulating subtypes (<0.4% TWC)


Dc based therapy

DC developed from patient monocytes

Pulsed with target antigens

Stimulated to maturation and inoculated back into patient

Tumour-specific immune responses measured

DC-based therapy

Currently in Phase II and Phase III trials for melanoma, prostatic carcinoma and lymphoma.


Common Myeloid Progenitor

Haemopoietic

Stem Cell

Circulating

Myeloid DC

Monocyte

CD34+

Stem Cell

Ex vivo GM-CSF + IL-4

Immature mdDC

Ex vivo GM-CSF +

Flt-3 + TNF

Maturation factors

Mature mdDC

CD34+ DC

Dendritic cell sources for therapy

Copland et al (2005) Cancer Immunol. Immunother. 54:297



N o4 adoptive immunotherapy
N.o4 vaccineAdoptive immunotherapy

Definition:

Induce, activate or multiply the anti-tumor effective cells invitro.Then transfuse the cells to thepatients to cause anti-tumor function .


Common anti tumor effective cells
Common anti-tumor effective cells vaccine

  • LAK (lymphokine-activated killers)

  • TIL (tumor infiltrating lymphocytes) :higherspecificity

  • CD3AK (CD3 antibodty activated killers)

  • CTL cell


复发 vaccine

免疫治疗

手术

肿瘤消失

另一侧新生肿瘤



N o 5 cytokine therapy
N.o 5 Cytokine therapy vaccine

The mechanism of cytokine therapy for tumor is that after being injected into body , the cytokine can regulate and increase the activity of immune cells ,and have enhance anti-tumor effect.

So far, IL-2,IFN-r,TNF-a and CSF have been used for tumor treatment .


N o 6 gene therapy

N.o 6 vaccineGene therapy

Tumor cells may lose some genes or express abnormal genes . Transduce target gene to body and restore the function of tumor cells help them to express normal products.


New pathways--gene therapy vaccine

  • Cytokines gene(IL、IFN、TNF)

  • Tumor Ag gene

  • MHC gene

  • Co-stimulatory molecule gene(B7)

  • Tumor suicide gene

  • anti-oncogene



Thank you! vaccine

See you!


Common anti tumor effective cells1
Common anti-tumor effective cells vaccine

  • LAK (lymphokine-activated killers)

  • TIL (tumor infiltrating lymphocytes) :higherspecificity

  • CD3AK (CD3 antibodty activated killers)

  • CTL cell


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