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Gene therapy for NKTI Feb2013
1. GeneTherapy
for the
Treatment of Cancer
AMY G. DY, MD, FPPS, FPSPO, FPSO
Pediatric Oncologist, NKTI
Head, Pediatric Hematology-Oncology
St. Luke’s Global City – Cancer Institute
3. Migs’ Story
2009
11 years old, boy, Filipino
Painless blood in urine
Cystoscopy: bleeding mass in bladder
Dx: Rhabdoid tumor of the urinary bladder
Tx: Partial removal of urinary bladder
4. Migs’ Story
Hospital in China
Locoregional and systemic chemotherapy
(Gemcitabine/Cisplatin)
Immunotherapy
2 mos: pelvic recurrence
Cryosurgery
Brachytherapy
5. Mig’s story
Progressive and metastatic
disease
(R) flank pain
Came back to Philippines
Urologist: total excision of bladder and
rectum
6. Mig’s story
Feb 2011
Gendicine: IT 9
IA 2
IV 1
+ 6 Chemo (ICE)
Outcome: No tumor seen on 2nd
look surgery
PET CT : no active disease
7.
8. OUTLINE
WHAT IS A GENE?
HOW IS GENE MEDICINE MADE?
HOW DOES IT WORK?
HOW IS IT USED?
OTHER CASES
15. P53 tumor suppressor gene
when a cell's
DNA is
damaged, it
acts as an
"emergency
brake" to stop
the resulting
cell division
that can lead
to cancer.
16. P53 tumor suppressor gene
It also acts as
an
executioner,
programming
damaged cells
to self-destruct
before their
altered DNA
can be
replicated.
17. P53 tumor suppressor gene
when it mutates, p53 can lose its
suppressive powers or have the
devastating effect of actually
promoting abnormal cell growth
p53 is the most commonly mutated
gene found in human tumors
27. The p53
protein
causes the
cancer cell to
self destruct
without
affecting
surrounding
normal cells
28. p53-Dependent Genep53-Dependent Gene
FunctionsFunctions
Apoptosis – a kind of programmed cell death
mediated by specific p53-dependent genes
Cell cycle arrest – “stressed” cells that tend to enter
mitosis get arrested (stop dividing)
DNA repair – if “stress” involves DNA damage, repair
function genes go into action
Differentiation/senescence—genes that limit
ability of cells to divide indefinitely are called to action
Autophagy-a kind of “self” eating that leads to cell
death
29. Other p53 functionsOther p53 functions
Down-regulation ofVEGF (vascular
endothelial growth factor) – prevents
angiogenesis in tumors.
Down-regulation of MDR1 (multidrug
resistance gene 1) – wt p53 actively
suppresses MDR1, certain p53 mutants
stimulate MDR1 and other genes, thus
decreases resistance to chemotherapy and
radiotherapy.
35. P53 Gene Therapy is Safe
• First used since year 2003
• Over 16,000 patients already treated
• No serious side effects
• Common side effect is self-limited fever
41. Case #2: JCG, 14yo/M
Osteosarcoma, metastatic to
lungs
Gendicine: IT 1
IA 5 primary
3 bronchial art
IV 10
(+ 2 chemo)
Outcome: 98% tumor necrosis
stopped treatment
42.
43.
44. Case #3: IR, 14 yo/M
secondary non-Hodgkin
lymphoma, st III
Gendicine: IT 6
IV 6
(+ 3 chemo)
Outcome: Normal PET scan
45. IR, 14 y.o. male sNon-Hodgkin lymphoma Stage III
March 3, 2011 March 15, 2011
AP
46. March 3, 2011
March 15, 2011
IR, 14 y.o. male
sNon-Hodgkin
lymphoma Stage
III
SAGITTAL
47. IR, 14 y.o. male sNon-Hodgkin lymphoma Stage III
March 3, 2011 March 15, 2011
TRANSVERSE
48. SUMMARY OF PEDIATRIC PATIENTS
1. FMZ 13 yo/M rhabdoid tumor st 4 CR
2. IR 14 yo/M sNHL St 3 CR
3. JCG 14 yo/M OS, mets (stopped tx)
4. DM 4 yo/M RMS
5. GP 7 yo/F Pontine glioma
6. EV 15 yo/M Ewing sarcoma st 4 PR
7. TAV 16 yo/M OS, mets
8. RT 7 yo/M Undiff sarcoma st 4 PR
9. FAV 3 yo/M Neuroblastoma St 4 PR
10.GHP 3 yo/F Ewing’s sarcoma St 3-4 CR
11.GL 4 yo/F Ewing’s sarcoma St 4 new
49. 22 ADULT PATIENTS
Breast ca - 6
Colon ca - 5
Rectal ca - 2
Lung ca - 2
Pancreatic ca - 1
Renal cell ca - 1
Esophageal ca - 1
Glioblastoma multiforme - 1
Uterine ca - 1
Malignant thymoma – 1
Pleomorphic spindle cell sarcoma - 1
51. Malignant Thymoma
•Dyspnea and hoarseness
(recurrent laryngeal nerve
palsy) – Nov 2011
•Unresectable mass; failed
chemotherapy
•12 X CT-guided
intratumoral injection
•No more dyspnea, voice
normal, back to work
52. Breast Cancer – chest wall recurrence
Dec 21, 2012
Jan 28, 2013
53. Summary of principles of p53 gene therapy:
1. advanced solid tumors
2. combined with conventional tx
3. direct tumor injection
4. 2-4 vials 2x a week
54. Liver Cancer
Male, 60 y.o.
•治疗前 before treatment 介入 + 基因治疗后 after interventional therapy+gene therapy