Evaluation of the Effect of HSV-tk/GCV Adenoviral Vector Vaccine Candidate in Inhibiting the Growth of Myeloma Tumors by Inducing Autophagy in BALB/c Mice

Multiple myeloma is the second most common blood malignancy which has remained incurable with current therapies. However, gene therapy using suicide viral vectors such as adenoviral vectors appear more promising than other treatments. The aim of this study was to evaluate the effects of an adenoviral vector vaccine candidate containing HSV-TK gene on tumor reduction and autophagy mechanism in animal model.

Myeloma tumor was created in mouse models using myeloma SP2/0 cell line. Three groups of negative control, positive control and target group of BALB/c mice were formed. Candidates for the Ad-HSV-tk /GCV vaccine at high titer (108) were then injected three times every 72 hours at target mice and metformin was injected into the control group for 12 consecutive days. Tumor size was measured in all 15 mice studied every three days, and finally, three days after the last dose of the vaccine, the tumors were removed for Western blotting and LC3B expression.

Examination of tumor size showed that injection of the vaccine and autophagy-inducing drug reduced tumor size compared to the negative control group. Western blotting indicated that LC3B expression was significantly higher in the target and positive control groups than in the negative control group. (Mean Diff: -0.4921; P value < 0.05; q: 7.911).

The results suggest that Ad-HSV-tk/GCV vaccine candidate was able to induce autophagy and reduce the growth of tumor cells in the animal model studied due to the ability of adenovirus to induce the immune system response, the anti-myeloma nature of adenovirus and the function of HSV-tk suicide gene