Transcript Cancer Gene Therapy

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 Vivo
 Which cells are the target cells

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.
Vectors
The way you insert the “normal” gene in
the patient’s cell is by vectors.
 The most common vectors that are used in
gene therapy are virus vectors

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
Types Of Viruses…
Retrovirus
 Adinovirus
 Lentiviruses
 Poxviruses
 and Herpes Viruses

Adenovirus
36 kb Double Stranded DNA Genome
Entry through CAR receptor and integrin co-receptor
E1A E1B
ITR 
L1
Stuffer DNA
E2B
L2
L4
L3
Therapeutic
Transgene
E2A
E3
L5
ITR
Stuffer DNA
E4
Latest Generation Adenoviral Vector
“Gutless”; Helper-dependent; Minimal Ad
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 cell’s DNA permanently
or temporarily

Strategies for Transgene Delivery
Ex Vivo
Cells removed from body
Transgene delivered
Cells cultured
Cells returned to the body
In Vivo
Transgene delivered
directly into host
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
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”
Gene Therapy Principles
AAV
Nucleus
Adenovirus
Therapeutic
Protein
Retrovirus/Lentivirus
Naked DNA
Target
Cell
Adenovirus Cell Entry
p53 Pathway
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
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
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%)

Results Not That Good
57% of the patients showed that the
cancer progressed to worse stages
 Why?

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

Cont: Major Problems that
Scientists Must Overcome
Deliver genes to a precise location in the
patient’s DNA
 Ensure that transplanted genes are
precisely controlled by the body’s normal
physiologic signals
