GENE THERAPY

GENE THERAPY FOR ORAL CANCER

WHAT IS A CANCER?

Cascade of cellular events that changes normal cell into malignant.

6th most worldwide – oral cancer.

OSCC most common , poor prognosis of max 5 year survival rate

WHAT IS GENE THERAPY?

Refers to replacing or repairing a defective gene in the diseased cell's genome in order to restore normal cell function and tissue integrity.

GENETIC BASIS OF OSCC

COMMMON GENE ALTERATIONS IN OSCC

GENE FUNCTION

TUMOUR SUPPRESSOR GENE

1. p16 senescence , cell cyle progression

2. p53 cell cyle regulation

3. PTEN signaling , migration

4. Rb gene cell cycle regulation

PROTOONCOGENES

1. CyclinD1 cell cycle regulation

2. Epidermal growth factor cell proliferation

3. p63 unknown

TYPES OF GENE THERAPY

GERMLINE GENE THERAPYGERMLINE GENE THERAPY

SOMATIC GENE THERPYSOMATIC GENE THERPY

GERM LINE THERAPY

SOMATIC THERAPY

Gene insertion Into germ cells into body cells

Modification Inherited by offspring

Restricted to individual

Safety Not ethically safe

Ethically sound & safe

STEPS IN GENE THERAPY

Identification and amplification of affected gene

Extraction and invitro culture

Transfer of therapeutic gene via vector

Transfer of corrected gene into the patient.

MODES OF TRANSMISSION

TECHNIQUES OF GENE THERAPY

GENE ADDITION THERAPY

Regulates tumour growth

Addition of tumour suppressor gene

p53

Induce apoptosis

GENE EXCISION THERAPY

Inhibits tumour growth

Removes defective oncogene

Egr-1(Early growth response factor)

Inhibits cell division

ANTI-SENSE RNA THERAPY

Gene expression inhibited by RNA.

Prevents activity of oncogenes – myc , ras and fos.

Inhibits virus – HPV1 , HTLV . HSV1.

SUCIDE GENE THERAPY

Genes are introduced – stimulates generation of products – toxic to the tumour cells.

Enables prodrug to active cytotoxic drug

IMMUNE THERAPY Increases patients immune

response to fight tumour

Increases efficacy of NK cells , T cells and cytokines

TYPES : 1.Therapeutic cancer vaccines

2.Monoclonal antibodies

3.Checkpoint inhibitors

4.Cytokines

PATHOPHYSIOLOGY OF IMMUNE THERAPY

GENE THERAPY BY ONCOLYTIC VIRUS Effective therapy

Virus are genetically modified

Which replicates & lyses tumour cells

Virus – HSV , chiefly Adeno virus

Adeno ONYX -015 lacks del of E1B region , contains p53

ADENO VIRUS : KEY VECTOR

UNIQUE viral structure

Capacity to hold large segments of DNA.

Easy manipulation

Produce high titers

Doesn’t integrate in the genomes

High transduction efficacy.

ADVEXIN Adenovirus type5 , E1 region

replaced by cDNA p53gene.

On introduction , cell growth arrests , apoptosis of tumour cells

Advexin intratumoural + Chemotherapy (Cisplastine , 5-flouracil ) + immunotherapy = positive result.

ONYX dl1520 Replicational condition virus ,

lacks E1B region , binds to & inactivates p53.

Tumour cells(p53 deficient) , allows rapid viral replication and kills tumour cells.

ONYX mouthwashes efficient – epithelial dysplasia and leukoplakia.

DEMERITS OF GENE THERAPY

Increased potentiality for toxicity & inflammatory response

Effectiveness of therapy can be reduced by host immune response

Intro of DNA in wrong place of genome – induce a tumour

Long term treatment

Technique sensitive

MERITS OF GENE THERAPY

Better prognosis

Targets specifically tumour cells

Cost effective

Lesser painful and discomfort

CONCLUSION

ONGOING RESEARCH IN LABORATORY AND CLINICS

PRESENT – ALTEREDADENOVIRUS+CHEMOTHERAPY+IMMUNOTHERAPY =POSITIVE RESULT

FUTURE AND BETTER SCOPE OF TREATMENT