Research on New Gene Therapies for Lung Cancer: This study is testing suitable AAV vectors in the laboratory that are designed to specifically target tumor cells in non-small-cell lung cancer (AH-OI-02 study).

Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer and can be treated with surgeries such as a lobectomy (removal of a lobe of the lung) or a segmentectomy (removal of a section of the lung). This is possible if the tumor is detected early, there are no distant metastases in other organs, and the patient’s overall health permits surgery. Surgery is particularly advisable when the tumor is confined to a specific area of the lung and complete removal appears feasible. Since tumor tissue is removed during these procedures anyway, this tissue is particularly well-suited for experimental research without affecting the patients’ treatment.

Gene therapy is a relatively new approach in cancer treatment that aims to deliver therapeutic genes directly into cancer cells to inhibit tumor growth or specifically destroy the tumor cells. So-called gene carriers (vectors) are used for this purpose; they serve as transport vehicles and deliver the genetic information to the target cell. AAV vectors (adeno-associated viruses) are used particularly frequently in this context. These are harmless viruses that do not cause disease in humans. They are generally well tolerated and trigger only minimal immune responses. Since tumor cells differ from one another depending on tissue type and origin (including surface characteristics and blood supply), it is necessary to identify suitable AAV vectors for each specific type of tumor. In the laboratory, the surface structures of these vectors can be modified in a targeted manner so that they “fit” specific tumor cells better. Since tumor cells vary greatly depending on their origin, the most suitable vectors are tested for each type of tumor. A vector that works for liver or colorectal cancer may be ineffective for lung cancer. AAV vectors are already approved for use in treating some rare genetic disorders (e.g., spinal muscular atrophy), but are not yet routinely used in cancer treatment.

The goal of this basic research study is to identify, from a wide range of AAV vectors, those variants that are particularly effective at penetrating tumor cells in non-small cell lung cancer (NSCLC). The long-term goal is to develop vectors that reliably reach the tumor tissue and can be used systemically (distributed throughout the body via the bloodstream) in future treatments. The removed tumor tissue is perfused in the laboratory with a fluid containing various AAV vectors (“ex vivo perfusion”). Subsequently, the study will determine which AAV vectors are most effective at penetrating the lung cancer cells. The study is for basic research and will not alter the actual treatment of the participating patients.

Eligible participants are women and men aged 18 and older with previously untreated non-small cell lung cancer (NSCLC) with a tumor size of at least 2 cm, who are scheduled to undergo a lobectomy or segmentectomy.