Laboratory study to identify vectors for targeted gene therapy in liver metastases

Liver metastases occur when tumor cells break away from the original tumor—for example, in the colon—and travel through the bloodstream to the liver, where they form new tumor sites. They are particularly common in colorectal cancer, but other types of cancer can also lead to liver metastases. Standard treatment usually consists of a combination of surgery, chemotherapy, and—in some cases—radiation therapy. In a hemihepatectomy, an entire half of the liver is surgically removed to eliminate as many liver metastases as possible and reduce the tumor burden in the body. Since the tumor tissue is removed during such procedures anyway, it is particularly well-suited for scientific research without affecting the actual treatment of the patients.

Gene therapy is a relatively new approach in cancer treatment that aims to deliver genetic material directly to tumor cells to inhibit tumor growth or destroy the tumor cells. Gene vectors are used for this purpose, designed to transport the genetic information specifically to the tumor cells. Adeno-associated viruses (AAV vectors) are particularly commonly used because they are generally very well tolerated and, by their very nature, rarely trigger immune reactions. There are many different AAV vectors whose envelope proteins can be easily modified, allowing them to be “adapted” to tumor cells through an evolutionary process. Since tumor cells differ from one another depending on tissue type and origin (e.g., surface characteristics, blood supply), it is necessary to find suitable AAV vectors for different types of tumors. A vector that works well for liver metastases may be less effective for tumors of the lungs or kidneys. AAV vectors have not yet been approved for the treatment of cancer, but are already being used for certain inherited diseases (e.g., spinal muscular atrophy and Leber’s congenital amaurosis).

The goal of the AAV-AH-OI-03 study is to identify, from a wide range of AAV vectors, those variants that are particularly effective at penetrating tumor cells. The goal is not only to find a vector for a single tumor, but also to identify vectors that work as reliably as possible in liver metastases, so that many patients could benefit from them. In the long term, this could lead to the development of vectors that are administered systemically—that is, via the bloodstream—and specifically target tumor tissue in the liver. To this end, tumor tissue from participating patients, which would be removed anyway, will also be used for laboratory analysis. In the laboratory, the removed tumor tissue is flushed through (“ex vivo perfusion”) to determine which AAV vectors are best able to penetrate tumor cells. The study is intended for basic research and may eventually lead to changes in treatment guidelines for future patients. The study is intended solely for basic research and will have no impact on the treatment of participating patients.

Women and men aged 18 and older with at least one untreated liver metastasis measuring at least 1.5 cm in size are eligible to participate in the study. A planned hemihepatectomy to remove the metastasis is a prerequisite.