Hepatocellular carcinoma (HCC) is a rapidly progressing cancer of the liver, and one of the most common tumors worldwide. When diagnosed early, liver transplant is a treatment option but most cases are detected at later stages when treatment options are fewer and survival times are reduced. HCC causes more than 650,000 annual deaths worldwide, about half of these occur in China. HCC risk increases due to behavioral (alcoholism, Type 2 diabetes), infectious (Hepatitis B or Hepatitis C virus infection) and genetic (alpha-1 anti-trypsin deficiency, hemophilia) factors.

HCC is a compelling case for developing genetic medicines in cancer therapy. This disease progresses rapidly even with the most effective chemotherapy, and later stage patients usually are not eligible for liver transplantation.

AGT is pursuing a two-arm strategy for HCC therapy. Lentivirus vectors will deliver genetic medicines that both disable key drivers of tumor growth or immune evasion, and activate the body’s tumor immunity mechanisms for active cancer suppression. With our early success in mouse models for cancer, we see opportunities to treat HCC and relieve suffering from this devastating disease. AGT anticipates beginning stage 1 clinical trials in 2018.

Liver Cancer Therapeutic Results from AGT Mouse Tests

Examples of control (untreated) tumors and AGT treated tumors in their host mice are shown below:


The mice shown are from the control group (on left) that were infected with the same tumor cells as the treatment group (on right) on the same date.  The initial tumors were about 0.5 cm in size before treatment was initiated. For the untreated mice, the tumors grew quickly (as illustrated in the control group, above left).  These mice are indicative of their groups (control and treatment), and show intermediate results of the test which are visually recognizable.

Liver Cancer Therapeutic Lentivirus

Potent anti-tumor efficacy by AGT’s therapeutic lentivirus in mice in vivo test

In vivo testing was performed after in vitro validations of our therapeutic lentivirus constructs.

HepG2 liver cancer cells were injected subcutaneously into nude mice. When the tumors grew to the size of  ~100mm3 , AGT therapeutic lentivirus or vehicle control was injected intratumorally at days 1, 4, 8, and 11. The tumor sizes were continuously monitored after treatment for an additional three weeks.

Observations: The AGT therapeutic lentivirus demonstrated potent anti-tumor efficacy. As shown in the figure, tumors treated with the AGT virus were eradicated. Tumor remission persisted throughout the three week post-treatment observation period. In contrast, tumors in the control groups increased rapidly. (Vehicle control: the formulation solution without lentivirus; Empty LV: a reporter lentiviral vector without anti-tumor components)

Research Collaborator associated with our work on Liver Cancer

Dean W. Felsher, MD