Radiation Immunomodulatory Gene Tumor Therapy of Rats with Intracerebral Glioma Tumors

Abstract

Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumors, single-fraction radiation therapy with 5 or 15 Gy had no significant effect on the survival time. Immunization with IFN-gamma-transfected N29 cells significantly increased the survival time by 61%. Single-fraction radiation therapy with 5 Gy combined with immunization increased the survival time significantly by 87% and complete remissions by 75% while with 15 Gy the survival time increased 45% with 38% complete remissions. For intracerebral N32 tumors, single-fraction radiation therapy with 15 Gy increased the survival time significantly by 20%. Immunization by itself had no significant effect with IFN-gamma-transfected N32 cells, but combined with 15 Gy single-fraction radiation therapy it increased survival time significantly by 40%, although there were no complete remissions. Based on these findings, we suggest a new therapeutic regimen for malignant glioma using single-fraction radiation therapy with a target absorbed dose of the order of 5-10 Gy combined with clinically verified immunotherapy.

Radiation Immune Modulation Therapy of Glioma

“…The surviving animals showed acquired antitumor immunity by rejecting challenge tumours (Newcomb, et al 2006). These results are in good agreement with the results of (75 %) long term survivals and acquired antitumor immunity in N29 rats treated with the combination of radiation and immune therapy with cells secreting IFN  (B. R. R. Persson, et al 2010).…”

“…The high efficiency of the combined treatment was maintained even under suboptimal conditions when neither of the individual modalities alone cured any of the mice (Lumniczky, et al 2002). Their results are in good agreement the survival rate of 75% (p<0.05) achieved in the Lund study of N29 tumours in rats treated with IFN- secreting vaccine combined with 5 Gy single fraction RT (B. R. R. Persson, et al 2010). …”

“…Further there were significant numbers of complete remissions of the most infiltrative N29 tumour implanted in Fischer-344 rats (B.R.R. Persson, et al 2010). Other researchers have also reported substantial tumour regression by single fraction radiation therapy combined with various regimes of immune therapy (Bradley 1999;Chakraborty, et al 2003;Demaria, et al 2005a;Friedman 2002;Garnett, et al 2004;Graf, et al 2002;Lumniczky, et al 2002).…”

“…So far only preclinical studies of hypofractionated radiation therapy in combination with immune therapy have been performed. The results are however encouraging and clinical trials using this therapeutic regime is urgently needed for both primary and recurrent glioma (Newcomb, et al 2006; B. R. R. B. R. R. Persson, et al 2010; B. R. R. Persson, et al 2008).…”

“…Currently, there is a growing interest in combining radiation with other kinds of therapy, of which some are immunotherapy, to treat a broad range of malignancies (Chakraborty, et al 2004;Gulley, et al 2005;Sharp, et al 2007). There is also an ongoing pre-clinical search for methods to enhance the therapeutic response of malignant glioma by combining immunotherapy with single fraction or hypo-fractionated radiation therapy (Demaria, et al 2005a;Graf, et al 2002;Lumniczky, et al 2002;Newcomb, et al 2006; B. R. R. ; B. R. R. Persson, et al 2003; B. R. R. Persson, et al 2010; B. R. R. Persson, et al 2008). The clinical trials using this approach, however, are still very sparse.…”