1. Powerpoint Templates Page 1 Powerpoint Templates Gene therapy for melanoma By Mohammed razeeth.S

2. Powerpoint Templates Page 2 Introdution Malignant melanoma is the most aggressive type of skin cancer characterized by the uncontrolled growth of melanocytes Melanocytes is the pigment producing cells of the skin Malignant melanoma is treatable if diagnosed at an early stage but currently the prognosis is poor

3. Powerpoint Templates Page 3 melanoma

4. Powerpoint Templates Page 4 gene therapy of melanoma Foreign genes are introduced into either tumor cells or the host’s immune cells To induce suicide of tumor cell or stop proliferation of tumor cells Production of cytokines

5. Powerpoint Templates Page 5 Goal of gene therapy targeted to melanoma cells To introduce “suicide”genes To transfer tumor suppressor genes To inactivate aberrant oncogene expression To introduce genes encoding immunologically relevant molecules

6. Powerpoint Templates Page 6 Gene therapy targeted to melanoma cells Introduction of “suicide” genes –Herpes simplex virus thymidine kinase gene(HSVtk) Transfer of tumour suppressor gene –P53 gene –p16INK4a

7. Powerpoint Templates Page 7 Gene therapy targeted to melanoma cells Inactivation of oncogenic signalling pathway. –ras –c-myc –Signal transducers and activators of transcription 3(stat 3)

8. Powerpoint Templates Page 8 Gene therapy targeted to melanoma cells Introduction of genes encoding immunologically relevant molecules –Allogenic MHC class I genes –Cytokine genes(GM-CSF, IL-2,IFNs, etc) –Co stimulatory molecules

9. Powerpoint Templates Page 9 Introduction of Suicide Genes Into Melanoma Cells Introduced of Suicide Genes into tumor cells Have the capacity to convert a nontoxic prodrug into a toxin within the tumor cell the herpes simplex virus thymidine kinase (HSVtk) gene

10. Powerpoint Templates Page 10 Introduction of Suicide Genes Into Melanoma Cells Drug ganciclovir is an acyclic nucleoside analogue when phosphorylated by HSVtk, is incorporated into DNA as ganciclovir triphosphate Resulting in the termination of DNA elongation during S-phase of transduced tumor cells

11. Powerpoint Templates Page 11 Transfer of Tumor Suppressor Genes Replacing defective tumor suppressor genes is the p53 gene Cirielli et al19 used an adenoviral vector to induce overexpression of wild-type p53 in either murine B16 melanoma or human SK-MEL-24 melanoma cell lines Resulted in apoptosis & inhibition of tumor growth

12. Powerpoint Templates Page 12 Blockade of Oncogenic Signaling Pathways

13. Powerpoint Templates Page 13 Insertion of Genes Encoding Cytokines Direct intratumoral or peritumoral injection of vectors expressing IFN-γ Result in the induction of local as well as systemic antitumor immune responses against melanoma It is antiproliferative and immunomodulatory effect

14. Powerpoint Templates Page 14 Macrophage interaction

15. Powerpoint Templates Page 15 Q session

16. Powerpoint Templates Page 16 Thank you