powerpoint templates page 1 powerpoint templates gene therapy for melanoma by mohammed razeeth.s
TRANSCRIPT
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Powerpoint Templates
Gene therapy for
melanoma
ByMohammed
razeeth.S
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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
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melanoma
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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
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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
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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
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Gene therapy targeted to melanoma cells
• Inactivation of oncogenic signalling pathway.– ras– c-myc– Signal transducers and activators of
transcription 3(stat 3)
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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
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Introduction of Suicide Genes IntoMelanoma 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
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Introduction of Suicide Genes IntoMelanoma 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
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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
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Blockade of OncogenicSignaling Pathways
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Insertion of Genes EncodingCytokines
• 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
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Macrophage interaction
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Q session
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Thank you