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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