Abscopal effect on subcutaneously radiation therapy; and/or Bertil R.R. Persson1,4), Dept. Radiation Physics1), Biomedical Centre, Lund University, 221 85 LUND, Sweden

implanted tumors (N29 glioma) immunization tumor cells. Catrin Bauréus Koch1,4), Gustav Grafström1,4), Crister Ceberg1,4), Dept of Tumor Immunology2) , Dept of Neurosurgery3) Rausing Laboratory4),

in rats treated with combined Henrietta Nittby3,4), Bengt Widegren2,4) and Leif G. Salford3,4). Contact: bertil_r.persson@med.lu.se RRS 2009 Bertil_R.Persson@rmed.lu.se

The Abscopal effect was studied in a rat model with N29 glioma cells subcutaneously implanted on both hind legs of Fischer-344 rats. The exponential tumor growth rate (TGR % per day) was estimated by consecutive measurements of tumor size. The Abscopal effect was evaluated by comparing the average tumor growth rate of the unirradiated tumors in the groups of treated rats, TGRtreat , with average TGRCtrl of the corresponding tumors in the group of untreated controls. Radiation therapy (RT) was given to the right lateral tumor with 60Co gamma radiation at 4 daily fractions of 5 Gy. Immunization was performed by weekly i.p. injections of syngeneic IFN secreting N29 cells. RRS 2009 Bertil_R.Persson@rmed.lu.se

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Controls RRS 2009 Bertil_R.Persson@rmed.lu.se

Immunotherapy RRS 2009 Bertil_R.Persson@rmed.lu.se

Radiation therapy RRS 2009 Bertil_R.Persson@rmed.lu.se

Radiation and Immunotherapy RRS 2009 Bertil_R.Persson@rmed.lu.se

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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) RRS 2009 Bertil_R.Persson@rmed.lu.se

Tumour growth rate of subcutaneous N29 tumours: Controls and after treatment with PEF, RT, IFN immunization or their combination RRS 2009 Bertil_R.Persson@rmed.lu.se

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 RRS 2009 Bertil_R.Persson@rmed.lu.se

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 LEFT SE Right N t ctrl H t Ctrl /V t H/V Controls 9.1  0,3 8.5  0.3 40 NS INFg 9.2  0,8 7.6  0.6 19 RT 6.1  0.4 4.5 15 <0.001 <0.01 RT +INFg 6.4  0.5 5.9 7 RRS 2009 Bertil_R.Persson@rmed.lu.se

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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 RRS 2009 Bertil_R.Persson@rmed.lu.se

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. RRS 2009 Bertil_R.Persson@rmed.lu.se

Specific therapeutic effect of subcutaneous N29 tumors after RT, Immunization with IFN and their combination RT+ IFN RRS 2009 Bertil_R.Persson@rmed.lu.se

In the present study the radiation induced abscopal effect was not significantly affected by immunization therapy, which might indicate that mechanisms other than immunogenic might be involved in the abscopal response. RRS 2009 Bertil_R.Persson@rmed.lu.se

THE END RRS 2009 Bertil_R.Persson@rmed.lu.se

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R I G T T RADIO IMMUNO-GENE TUMOUR THERAPY Bertil R.R. Persson PhD, MD h.c. Professor of medical radiation physics Lund University, 221 85 LUND Sweden

Abscopaleffect in subcutaneously implanted tumors (N29 glioma) in rats treated with combined radiation therapy; and/or immunization tumor cells. Abscopal effect on subcutaneously contra-lateral treatments with radiation therapy and immunization with syngeneic interferon-gamma secreting tumor cells.

Biomedical Centre, Lund University, 221 85 LUND, Sweden Bertil R.R. Persson1,4), Catrin Bauréus Koch1,4), Gustav Grafström1,4), Crister Ceberg1,4), Henrietta Nittby3,4), Bengt Widegren2,4) and Leif G. Salford3,4). Dept. Radiation Physics1), Dept of Tumor Immunology2) , Dept of Neurosurgery3) Rausing Laboratory4), Biomedical Centre, Lund University, 221 85 LUND, Sweden Contact: bertil_r.persson@med.lu.se

Radiation therapy (RT) RRS 2009 Bertil_R.Persson@rmed.lu.se

N29 tumours inoculated Subcutaneously on both sides 200 000 cells 50 000 cells Only the right tumour was irradiated RRS 2009 Bertil_R.Persson@rmed.lu.se