Effect of GM-CSF on tumor-specific immune response and antitumoral efficacy when combined with suicide gene therapy

Abstract

e14610 Background: Suicide gene therapy is one of the promising treatment modalities in cancer treatment. Combination of an immunotherapy modality with suicide gene therapy would increase the tumor eradciating efficacy of either treatment strategy used alone. Methods: In the current study, we constructed adenoviral vectors carying ytosine deaminase (CD), granulocyte macrophage-colony stimulating factor (GM-CSF) vectors. We tested the in vitro efficacy of the vectors in both human and mouse tumor cell lines and in a syngeneic mouse model of colon cancer with tumor explants of CRL 2638 cells. Results: Our results show that the vectors carrying CD/GM-CSF transcription units are effective in terms of killing of tumor cells when 5-FC added. Addition of GM-CSF transgene induced a significant amount of GM-CSF secretion (250 pg/ml/105 cells) of infected cells. In the syngeneic colon cancer model, addition of GM-CSF significantly increased tumor-specific cellular immune response when compared to suicide gene therapy alone. (p<0.01). Likewise, GM-CSF addition caused a 8 times reduction in the ratio of Tregs infiltrating the tumor nodules (p<0.001). Accordingly, GM-CSF decreased the tumor growth by 2 times an d increased the median survival time by 50% (p<0.01). Conclusions: These impressive results of in-vitro cytotoxicity and encouraging results of in-vivo testing of the our newly constructed GM-CSF carrying vector suggest a potential for the use of the vector for the treament of established tumors by inducing tumor specific immune response. No significant financial relationships to disclose.