Gene therspy for melanoma

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Gene therspy for melanoma

  1. 1. Powerpoint Templates Gene therapy for melanoma By Mohammed razeeth.S
  2. 2. Introdution <ul><li>Malignant melanoma is the most aggressive type of skin cancer characterized by the uncontrolled growth of melanocytes </li></ul><ul><li>Melanocytes is the pigment producing cells of the skin </li></ul><ul><li>Malignant melanoma is treatable if diagnosed at an early stage but currently the prognosis is poor </li></ul>
  3. 3. melanoma
  4. 4. gene therapy of melanoma <ul><li>Foreign genes are introduced into either tumor cells or the host’s immune cells </li></ul><ul><li>To induce suicide of tumor cell or stop proliferation of tumor cells </li></ul><ul><li>Production of cytokines </li></ul>
  5. 5. Goal of gene therapy targeted to melanoma cells <ul><li>To introduce “suicide”genes </li></ul><ul><li>To transfer tumor suppressor genes </li></ul><ul><li>To inactivate aberrant oncogene expression </li></ul><ul><li>To introduce genes encoding immunologically relevant molecules </li></ul>
  6. 6. Gene therapy targeted to melanoma cells <ul><li>Introduction of “suicide” genes </li></ul><ul><ul><li>Herpes simplex virus thymidine kinase gene(HSVtk) </li></ul></ul><ul><li>Transfer of tumour suppressor gene </li></ul><ul><ul><li>P53 gene </li></ul></ul><ul><ul><li>p16INK4a </li></ul></ul>
  7. 7. Gene therapy targeted to melanoma cells <ul><li>Inactivation of oncogenic signalling pathway. </li></ul><ul><ul><li>ras </li></ul></ul><ul><ul><li>c-myc </li></ul></ul><ul><ul><li>Signal transducers and activators of transcription 3(stat 3) </li></ul></ul>
  8. 8. Gene therapy targeted to melanoma cells <ul><li>Introduction of genes encoding immunologically relevant molecules </li></ul><ul><ul><li>Allogenic MHC class I genes </li></ul></ul><ul><ul><li>Cytokine genes(GM-CSF, IL-2,IFNs, etc) </li></ul></ul><ul><ul><li>Co stimulatory molecules </li></ul></ul>
  9. 9. Introduction of Suicide Genes Into Melanoma Cells <ul><li>Introduced of Suicide Genes into tumor cells </li></ul><ul><li>Have the capacity to convert a nontoxic prodrug into a toxin within the tumor cell </li></ul><ul><li>the herpes simplex virus thymidine kinase (HSVtk) gene </li></ul>
  10. 10. Introduction of Suicide Genes Into Melanoma Cells <ul><li>Drug ganciclovir is an acyclic nucleoside analogue </li></ul><ul><li>when phosphorylated by HSVtk, is incorporated into DNA as ganciclovir triphosphate </li></ul><ul><li>Resulting in the termination of DNA elongation during S-phase of transduced tumor cells </li></ul>
  11. 11. Transfer of Tumor Suppressor Genes <ul><li>Replacing defective tumor suppressor genes is the p53 gene </li></ul><ul><li>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 </li></ul><ul><li>Resulted in apoptosis & inhibition of tumor growth </li></ul>
  12. 12. Blockade of Oncogenic Signaling Pathways
  13. 13. Insertion of Genes Encoding Cytokines <ul><li>Direct intratumoral or peritumoral injection of vectors expressing IFN-γ </li></ul><ul><li>Result in the induction of local as well as systemic antitumor immune responses against melanoma </li></ul><ul><li>It is antiproliferative and immunomodulatory effect </li></ul>
  14. 14. Macrophage interaction
  15. 15. <ul><li>Q session </li></ul>
  16. 16. <ul><li>Thank you </li></ul>

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