Immune gene therapy of cancer

Abstract

Cancer gene therapy emerged as a promising treatment modality 3 decades ago. However, the failure of the first gene therapy trials in cancer treatment has decreased its popularity. Likewise, immunotherapy has followed a similar course. While it was a popular and promising treatment with IL-2 and interferon and cancer vaccines in the 1980s, it later lost its popularity. Immunotherapy became one of the main options for cancer treatment with the successful use of immune checkpoint inhibitors in clinics approximately 10 years ago. The success of immunotherapy has increased even more with the introduction of cancer gene therapy methods in this area. With the identification of the oncolytic herpes simplex virus and Chimeric antigen receptor (CAR) T-cells, immune gene therapy has become an essential modality in cancer treatments such as surgery, radiotherapy, chemotherapy, and targeted therapies.

Keywords: Immunotherapy; cancer; cytosine deaminase; gene therapy; granulocyte-macrophage colony-stimulating factor.

Figure

The adenoviral construct carrying cytosine deaminase and GM-CSF genes under the control of a CMV promoter produces CD and GM-CSF in tumor cells. The 5-FU produced in the tumor cell with the help of CD from 5-florocytosine, an anti-mycotic drug, kills the tumor cell and cause tumor antigen shedding. At the same time, the GM-CSF produced by the vector in the tumor cell attracts dendritic cells nearby. The immature DCs uptake tumor antigens and present to T-cells in lymph nodes. The armed T-cells then enter the systemic circulation and fight against tumor cells wherever they meet. ( : Naïve T-cell, : Armed tumor-specific T- cell, : Immature dendritic cell, : Mature dendritic cell, : Tumor cell, Adenoviral vector carrying cytosine deaminase (yellow) and GM-CSF (blue) genes.)