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Title:

Cancer Gene Therapy

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Cancer Gene Therapy Using Tumor Suppressor Genes. Overview Gene Therapy p53 Using Gene Therapy to Treat Lung Cancer Problems Gene Therapy Vectors In Vivo vs. Ex ... – PowerPoint PPT presentation

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Title: Cancer Gene Therapy


1
Cancer Gene Therapy
  • Using Tumor Suppressor Genes.

2
Overview
  • Gene Therapy
  • p53
  • Using Gene Therapy to Treat Lung Cancer
  • Problems

3
Gene Therapy
  • Vectors
  • In Vivo vs. Ex Vivo
  • Which cells are the target cells

4
What is Gene Therapy?
  • Gene therapy is a technique for introducing the
    genetic material of a gene in a patient that
    lacks that gene because of a mutation.

5
Vectors
  • The way you insert the normal gene in the
    patients cell is by vectors.
  • The most common vectors that are used in gene
    therapy are virus vectors

6
Why Viruses?
  • Viruses through the time of evolution have
    evolved to infect the cells with great
    specificity
  • Viruses tend to be very efficient at transfecting
    their own DNA into the host cell genome.
  • This allows them to produce new viral particles
    at the period of synthesis of the cell

7
Types Of Viruses
  • Retrovirus
  • Adinovirus
  • Lentiviruses
  • Poxviruses
  • and Herpes Viruses

8
Adenovirus
36 kb Double Stranded DNA Genome
Entry through CAR receptor and integrin
co-receptor
9
L1
L2
L4
L3
L5
E1A
E3
E1B
E2A
E4
E2B
Latest Generation Adenoviral Vector Gutless
Helper-dependent Minimal Ad
10
Which Virus to Use?
  • Depends
  • how well they transfer the genes to cells
  • which cells they can recognize and infect
  • and whether they alter the cells DNA permanently
    or temporarily

11
Strategies for Transgene Delivery
Ex Vivo
In Vivo
Cells removed from body
Transgene delivered directly into host
Transgene delivered Cells cultured
Cells returned to the body
12
Which cells are the target cells
  • Both Healthy and Cancerous cells can be
  • a target
  • Ex of targeting Healthy cells
  • One way is by replacing a missing or altered gene
    with a normal one

13
Cont Which cells are the target cells
  • Ex of targeting Cancer Cells
  • Scientists can target cancer cells with genes
    that can be used to destroy the cells. In this
    technique, cancer cells are introduced to what is
    called suicide genes

14
Gene Therapy Principles
AAV
Nucleus
Adenovirus
Therapeutic Protein
Retrovirus/Lentivirus
Target Cell
Naked DNA
15
Adenovirus Cell Entry
16
p53 Pathway
17
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18
Using Gene Therapy to Treat Lung Cancer
  • In this clinical trial the scientist used gene
    therapy in combination with radiation therapy so
    they can treat lung cancer in 19 different
    patients

19
Treatment Gene therapy and Radiation.
  • Intratumoral needle injections of Ad-p53 on days
    1, 18 and 32 of the treatment.
  • tumors 4 cm where injected with 10 ml
  • tumors 4 cm were injected with 3 ml
  • Radiation therapy

20
Results
  • 17/19 patients made it through the entire therapy
  • complete response in 2 patients (11)
  • partial response in 4 patients (21)
  • stable disease in 1 patient (5)
  • progressive disease in 11 patients (57)

21
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22
Results Not That Good
  • 57 of the patients showed that the cancer
    progressed to worse stages
  • Why?

23
Major Problems that Scientists Must Overcome
  • Identify more efficient ways to deliver the genes
    to the patients genetic material
  • Develop vectors that can specifically focus on
    the targeted cells
  • Ensure that vectors will successfully insert the
    desired genes into each of these target cells

24
Cont Major Problems that Scientists Must
Overcome
  • Deliver genes to a precise location in the
    patients DNA
  • Ensure that transplanted genes are precisely
    controlled by the bodys normal physiologic
    signals
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