Immunogene Therapy

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Immunogene Therapy Adoptive T Cell Transfer In
The Treatment Of Cancer
Emmet O Brien Dept. of Surgery Supervisors Prof
G. O Sullivan Dr. Mark Tangney
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• rugs can only repress symptoms they cannot
  eradicate disease. The true remedy for all
  diseases is Natures remedy....
• There is at bottom only one genuinely scientific
  treatment for all diseases, and that is to
  stimulate the phagocytes. Stimulate the
  phagocytes. Drugs are a delusion.

George Bernard Shaw The Doctors Dilemma. 1906
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Immunogene Therapy

• Involves modulation of the tumour and the hosts
  immune response capacity
• Tumour immune evasion mechanisms
• T cell function anergy
• APCs, cytokines
• DNA Delivery Systems
• Non-viral
• Liposome low efficiency, toxic
• Viral Immunogenic, safety issues

T-cell (orange) killing a cancer cell (mauve)
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Background

• Successful immunogene delivery to growing tumours
  in the Cork Cancer Research Centre
• GM-CSF
• B7-1
• Gene delivery Plasmids
• Vector delivery Electroporation

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Aims

• pGT141 vs. pVivoGB
• To compare the efficacy of a novel plasmid coding
  for GM-CSF and B7-1 with the previously reported
  plasmid in the treatment of fibrosarcoma in a
  murine model
• Adoptive Transfer
• To investigate the potential of adoptive transfer
  of lymphocytes derived from cured animals in
  the treatment of established tumours in a murine
  model

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Methods 1

• BalbC mice
• JBS tumour culture
• Plasmid construction
• DNA preparation
• Megaprep
• Injection measurement
• Controls - JBS blank plasmid
• Electroporation

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Electroporation
Step 1
Step 2
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TcR
Ag
T - Cell
Tumour Cell
B7-1
CD28

GM-CSF
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Methods 2

• BalbC mice
• JBS tumour culture
• Tumour injection
• Initial flank
• Controls
• Naïve pGT141 cured BalbC mice
• Splenocyte harvesting
• Mix with JBS tumour cells
• Injection Measurement
• Opposite flank
• Controls

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T - Cell
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Results Plasmid Vectors
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Results Adoptive T-Lymphocyte Transfer
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Discussion

• Mammalian promoters
• CpG sequences
• Immunogene therapy is capable of producing a
  systemic anti-tumour response
• Proliferation of adopted lymphocytes in host
  mediating systemic immunity to tumour challenge
• Adoptive transfer promising

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Conclusion

• pVivo is as effective as pGT141 in the delivery
  of immunogenes in a mouse model
• Suitable vector for future research initiatives
• Immunogene therapy is sufficiently potent to
  effect an anti-tumour lymphocyte response
• Lymphocytes created are durable
• Capable of mediating an antigen-specific
  anti-tumour response on adoptive transfer to
  syngeneic mice

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Future?

• Immunogene T cell Transfer
• Sleeping Beauty
• Regulatory T cells
• Technological advancements
• Future cellular/gene discovery
• Clinical Trials?

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Questions?