Oncolytic viruses armed with immunostimulatory genes for cancer treatment

• Main Author: Šilanskas, Mantas
• Format: Others
• Language: English
• Published: Uppsala universitet, Institutionen för immunologi, genetik och patologi 2018
• Subjects: Cancer; Virus; Immunotherapy; Immunology; Immunologi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-353153

Cancer is a major health burden in modern society, costing millions of lives worldwide and negatively impacting many more. With increasing rates of cancer, there is a need for new approaches to its treatment. This is where immunotherapies step in, this a relatively new approach to cancer treatment which caught public’s attention only in recent years. The main goal of these therapies is to enhance and help immune cells to identify and kill tumor cells, thereby initiating the cycle of cancer immunity. In this project LOAd platform viruses were evaluated and compared for their ability to induce oncolysis in cancer cells and ability to produce immunostimulatory molecules. Established LOAd703 virus armed with CD40L and 4-1BBL transgenes was compared to new constructs LOAd732, LOAd780 and LOAd786. All three new viruses are armed with CD40L and 4-1BBL, but also have additional transgenes X, Y and Z, respectively. Specific molecules coded by these transgenes cannot be disclosed at this moment. All viruses demonstrated high competence in oncolysis of A549-lung, T24-bladder and 526-mel melanoma cancer cell lines and were able to express transgenes coding for CD40L and 4-1BBL in all cell lines. New viruses were able to induce expression of new transgenes in infected cells, except for LOAd780 infected cell which had low concentration of protein Y in their supernatants. Also dendritic cells matured using LOAd viruses were able to induce expansion of CMV-specific T cells and a major expansion of natural killer cells.