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Gene therapy in Cancer treatment
1.
2. Main Cause
◊ Mutations in its DNA
Reason
Exposure to Carcinogens (e.g. tobacco)
Exposure to Viruses
Epigenetic factors (e.g. tumour promoter
effects)
Activation of Proto- oncogenes to Oncogenes
Inactivation of Tumour Suppressor genes (e.g.
BRCA1 & 2)
3. Use of nucleic acids for treatment,
cure or prevention
Replacement of a defective gene with
its functional copy
4. » Main Types
1. Immunotherapy
2. Oncolytic Virotherapy
3. Gene Transfer
5. Uses GM cells and viral particles to
stimulate the immune system to destroy
cancer cells; e.g. lung cancer.
6.
7. Uses viral particles that replicate within the
cancer cell to cause cell death; e.g.
metastatic cancers.
8. Introduces new genes into a cancerous cell
or the surrounding tissue to cause cell death
or slow the growth of cancer; e.g. in solid
tumours.
10. by introducing specificity into T cells
Delivering CAR
Recognize antigen of
choice on cancer cells
Facilitate tumour cell
recognition
Formation of activated
T cells
Killing of Target cells Immunotherapy
11. By restoration of functional p53 using a
recombinant adenovirus expressing under a
Rous sarcoma virus promoter.
This is the first commercialized gene therapy,
named GendicineTM.
By in vivo intratumoural injection.
Gene Transfer
12. HSV-TKase (vector NV1020) has been used
to convert the prodrug Ganciclovir into
cytotoxic triphosphate ganciclovir.
Commercial example: Cerepro
(cytomegalovirus promoter).
Oncolytic
Virotherapy
13. Cancer Type Commercial
Name
Approach Type of Therapy
Prostate Cancer Prostvac TRICOM vector
vaccine
Immunotherapy
Soft Tissue
Sarcoma
TNFerade Adenoviral
vector
Gene Transfer
Pancreatic
Cancer
Rexin-G Retroviral vector Gene Transfer
14. Serenities
1. iPSC technology
2. Hope for orphan and other diseases
Concerns
1. Translation of iPSC technology into the
clinics
2. AAV immunogenicity
15. 1. Cross D and Burmester JK (2006), Gene Therapy for Cancer Treatment: Past,
Present and Future; Clinical Medicine & Research Volume 4, Number 3: 218-227
2. Kaufmann KB, Büning H, Galy A, Schambach A, Grez M; Gene therapy on the
move; EMBO Mol Med (2013) 5, 1642–1661
3. Das SK, Menezes ME, Bhatia S, Wang XY, Emdad L, Sarkar D and Fisher PB;
Gene Therapies for Cancer: Strategies, Challenges and Successes; J Cell
Physiol. 2015 February ; 230(2): 259–271. doi:10.1002/jcp.24791.
4. Baban CK, Cronin M, O’Hanlon D, O’Sullivan GC and Tangney M (2010); Bacteria
as vectors for gene therapy of cancer; Bioengineered Bugs 1:6, 385-394.