Genetically Engineered Adenovirus Stabilizes Pancreatic Tumors in Three Patients at Low Dose in Early Safety Trial

A genetically engineered adenovirus stopped pancreatic tumors from growing or spreading in three people in a US clinical trial, according to results presented by Masato Yamamoto at the annual meeting of the American Society of Gene and Cell Therapy in Boston, Massachusetts, earlier this month.

The first patient had a pancreatic tumor 7 centimetres across and received the treatment one year before the presentation. The other two patients were treated after the first patient.

At the time of treatment, the patients’ tumors had not spread beyond the pancreas. Since treatment, the three patients’ tumors have not grown further. The three patients are all still alive and have clinically stable disease, Yamamoto said.

The trial is an initial safety trial using one-tenth of the intended eventual dose. The virus is an adenovirus genetically engineered to replicate only inside tumors and not in healthy tissue. Viral replication is activated by the enzyme cyclooxygenase-2 (COX-2), which is present at much higher levels in cancer cells than in normal cells.

After infection, cancer cells burst open and die, releasing more virus that can infect neighboring cancer cells. The virus was injected directly into the patients’ tumors through a thin tube guided down the throat to the pancreas. The injection tube had an ultrasound probe on the end to visualize the tumors.

The tumors stopped growing but have not become smaller, possibly due to the low treatment dose, Yamamoto said. He thinks the tumors may start to shrink as the virus has more time to replicate. As tumor cells break apart, the immune system may recognize and attack the cancer.

Yamamoto leads the development of the viral treatment at the University of Minnesota. Another 15 patients will now be given higher doses to find the optimum level. Yamamoto thinks the treatment could potentially be effective against metastatic pancreatic cancer if the immune system recognizes and destroys tumor cells that have spread.

Yamamoto and colleagues are planning to combine the viral treatment with checkpoint inhibitor immunotherapies in future trials. Pancreatic cancer patients usually live only around three to six months after diagnosis once the cancer has spread. Pancreatic tumors have tough, fibrous exteriors that block chemotherapy drugs.

Immunotherapies are ineffective against pancreatic tumors because the tumors can hide from the immune system. Adenoviruses have been investigated as potential cancer treatments since the 1950s. In the 1950s, women with cervical cancer were injected with an unmodified adenovirus in a clinical trial with partial success.

T-VEC is the only cancer-killing virus approved by the US Food and Drug Administration. T-VEC is a genetically modified herpes simplex virus injected directly into melanoma tumors.