1. R E I G T T RADIO ELECTRO IMMUNO-GENE TUMOUR THERAPY
Bertil R.R. Persson PhD, MD h.c.
Professor of medical radiation physics
Lund University,
LUND Sweden

2. Abscopal effect on subcutaneously implanted N29 rat glioma tumours, from contra-lateral treatments with pulsed electric fields, radiation therapy and immunization with syngeneic interferon-gamma secreting tumor cells.

3. Biomedical Centre, Lund University,
Bertil R.R. Persson1,4), Catrin Bauréus Koch1,4), Gustav Grafström1,4), Crister Ceberg1,4), Bengt Widegren2,4) and Leif G. Salford3,4).
Dept. Radiation Physics1), Dept of Tumor Immunology2) , Dept of Neurosurgery3) Rausing Laboratory4),
Biomedical Centre, Lund University,
LUND Sweden
Contact:

4. EANO 6 May-2005

5. N29 tumours inoculated Subcutaneously on both sides
cells
cells
Only the right
tumour was
irradiated
EANO 6 May-2005

6. PEF treatment
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7. Radiation therapy (RT)
cells
Only the right
tumour was
Irradiated with
60Co  radiation
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8. Exponential Tumour Growth Model
Tumour growth rate “TGR” is estimated from the tumour volume measurements by fitting the data of each individual tumour to a model of exponential growth
where
“TVt” is Tumour volume at time t
t is time after first treatment.
“TV0” is Tumour volume at time t = 0,
“TGR” is tumour growth rate constant (% per day)
EANO 6 May-2005

9. Tumour growth rate of subcutaneous N29 tumours: Controls and after treatment with PEF, RT, IFN immunization or their combination
EANO 6 May-2005

10. Specific Therapeutic Effect “STE” is defined as follow.
The average of the individual Tumour growth rate constant in the group of exposed rats. day-1
The average of the individual Tumour growth rate constant in the group of control rats. day-1
EANO 6 May-2005

11. The STE is equal to 0 when the average of tumour growth rate constant of the exposed group, is equal to the average of the tumour growth rate constant of the control.
The STE is equal to 1 when the average tumour growth rate constant of the exposed group, is equal to 0.
EANO 6 May-2005

12. Specific therapeutic effect of subcutaneous N29 tumors after RT, Immunization with IFN and their combination RT+ IFN .
EANO 6 May-2005

13. Therapeutic Enhancement Ratio.
“TER” of the combined treatments is the ratio of the specific therapeutic effect “STE” of the experimental combination of Electrical pulses and radiation and the hypothetical combination of the two agents used independently
where the hypothetical specific therapeutic effect by independent (additive) action of ionizing radiation and Electrical pulses is given by
EANO 6 May-2005

14. Therapeutic Enhancement Ratio
“TER” is a measure of any synergistic or diminishing effect obtained in the combination of the two agents. TER > 1 may due to synergistic interaction of sub lethal lesions induced by both agents to produce more lethal events.
EANO 6 May-2005

15. EANO 6 May-2005

16. Intracerebral implanted N29 tumours
EANO 6 May-2005

17. The rat glioma models N29
Stereotactic implantation of 500 cells in in the brain (caudate n.)
6-7 weeks later,
a tumour (diam.
4-6 mm) giving
symptoms, has
developed
In vitro culture
of rat glioma cells
EANO 6 May-2005
Salford 99

18. Immunization against experimentally induced brain tumour
N29 brain tumour cells
N29 brain tumour cells
Transfected with IFN- gene
IMMUNIZATION
Stereotactic
injection of 5000 cells
Day 7
Radiation therapy
Day 0
Day 7, 21, 35
By ip incection
of 10 million cells
Day 100
2 out of 8
dead!
6 out of 7
dead
Day 100
Immuneresp
EANO 6 May-2005

19. Survival diagram for the different treatments
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20. Intracerebral implanted
N32 tumours
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21. Survival diagram for the different treatments
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22. Change in Mean survival time
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23. Table I. Tumour Growth rate ”TGR” of subcutaneous tumours implanted on both Right and Left hind leg. The right tumour was treated with radiation (RT). Average of all experiments
Resultat
Right SE N
LEFT
t ctrl H
t Ctrl /V
t H/V
Controls
8.5
 0.3 40
9.1
 0,3
0.1
INFg
7.6
 0.6 19
9.2
 0,8
0.3
0.9 RT
4.5 15
6.1
 0.4
10-10
10-6
0.003
RT +INFg
5.9
 0.5 7
6.4
0.002
0.0004
0,49
EANO 6 May-2005

24. Number of Survivals and mean survival time of intra cerebral tumours treated with IFN cell immunization, radiation therapy and their combination.
Date
Num. Survival /
Num. animals
Median
Survival time days
Significance
t test
Controls
1/6 60
Immunization with IFN-g
2/6
147
0.08
RT 5 Gy
0/8 45
0.2
RT 15 Gy
2/8 88
0.4
RT 5 Gy + Immunization 3x
6/8
154
0.01
RT 15 Gy + Immunization 3x
5/8
118
0.1
EANO 6 May-2005

25. Log TV of Controls
EANO 6 May-2005

26. Number of rats dead and alive in the various groups of treatment at 130 days after inoculation .
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27. Mean survival time at 130 days after inoculation in the various groups of treatment.
EANO 6 May-2005