Cancer theraapy at gene level

1. Cancer therapy at Gene Level
Dr. P. Suganya
Assistant Professor
Department of Biotechnology
Sri Kaliswari College (Autonomous), Sivakasi

2. Gene therapy is an experimental treatment
That involves genetic material
Into cells to give them a new function or
restore a missing function,
As cancer may be caused by damaged or
missing genes

3.  Gene therapy is designed to modify cancer cells at the molecular level and
replace a missing or bad gene with healthy one.
 The new gene delivered to the target cell via a ”vector” which is usually an
inactive virus or liposome
Therapeutic gene
The therapeutic exonucleic acid or DNA consist of
 the transcription unit of a therapeutic gene
 Regulatory sequences controlling transcription initiation and termination

4. Strategies for transgene delivery
 EXVIVO
Cells removed from body
Transgene delivered cells cultured
Cells returned to the body

5. INVIVO
Transgene delivered directly in to host
Gene delivery system
Biological
Genetically modified viral vectors

6.  Chemical Generation of liposomes from cationic lipids or
polymers
 Physical Direct injection – Electroporation or
Hydrodynamic technology

7. In vivo gene therapyS. No Type of cancer Tissues Gene
1 Brain Tumors Tumor cells HS-tk (GCV)
2 Brain Tumors Tumor cells Antisense IGF-1
3 Brain Tumors HSC MDR-1
4 Breast cancer Fibroblasts IL-4
5 Breast cancer HSC MDR-1
6 Colorectal cancer Tumor cells IL-2 or TNF
7 Colorectal cancer Fibroblast IL-2 or IL-4
8 Colorectal cancer Tumor cells HLA-B7+B2m
9 Malignant melanoma Tumor cell TNF or IL-2
10 Malignant melanoma Fibroblasts IL-4
11 Malignant Melanoma Tumor cell Alpha interferon
12 Malignant Melanoma Tumor cells B7co-stimulatory molecule
13 Malignant Melanoma Tumor cell HLA-B7 0r HLA-B7+b2m
14 Neuroblastoma Tumor cell IL-2
15 Non small cell lung cancer Tumor cell Antisense k-res WTp53
16 Ovarian cancer Tumor cell Hs-tk
17 Ovarian cancer HSC MDR-1
18 Renal cell carcinoma Tumor cell IL-2, TNF, GM-CSF
19 Renal Cell carcinoma Fibroblast IL-4
20 Small cell lung cancer Tumor cell IL-2
21 Solid tumor Tumor cell HLA-B7+B2m

8. HSC- Hematopoietic stem cell
TNF- Tumour Necrosis factor
GM-CSF- Granulocyte Macrophage- Colony
Stimulating Factor
B2n9- B2 Microglobulin

9. Exvivo Gene therapy
S. No Type of cancer Tissues Gene
1 Breast cancer Epithelial cell BRCA, BRCa2
2 Ovarian cancer Tumor cell BRCA, BRCA2
3 Leukemia WBC BCR-ABL
4 Melanoma Tumor cell BRAF and MEK
5 Lung Tumor Protein P53

10. Invivo gene therapy
Where the genes are changed or treated in
cells still in the body
Direct delivery of genes
In to the cells
Of a particular tissue in the body

11. Eg: Ovarian cancer-Hs-tk gene

12. Exvivo gene therapy
Transfer of gene into cultured
cells and reinsertion

14. Applications
 Exchange the immunogenicity of the tumor by inserting genes for cytokines,
allogeneic surface antigens, costimulatory molecules, inhibition of tumor
growth factor production with antisense IGF-1
 Genetically alter immune cells to increase antitumor efficacy by the insertion
of : immune stimulatory factors (eg:IL-2) or genes that encode antibody to
tumor specific receptor to enhance tumor immune cell interaction
 Insert a sensitivity or suicide gene into the tumor: Hs-tSV/GCV, cytosine
deaminase or 5-fluorocytidine, genes that disrupt DNA repair (Antisense DNA
Polymerase)
 Block encode expression, antisense, oligonucleotide ribozymes

15.  Insert tumor suppressor gene
 Genetically protect tissue from the systemic facilities of chemotherapy,
Unsertion of a MDR-1 gene

16. THANK YOU