FUNDED PROJECTS

In recent years, immunotherapy has emerged as a groundbreaking approach to cancer treatment, offering new hope to patients battling this disease. Despite its success, challenges remain, particularly in treating advanced solid tumors, which often resist current treatments.

This research project focuses on a novel approach in cancer immunotherapy, TCR-T therapy, targeting a specific mutation known as KRAS G12V, found mostly in lung, pancreatic, and colon cancers. This mutation is part of a group of genetic alterations that drive cancer growth and are notoriously difficult to treat effectively with current therapies.

Our team has made significant strides in identifying and validating a new potential treatment target—a small piece of protein, or neoantigen, directly created by the KRAS G12V mutation. We have successfully demonstrated that this neoantigen can be presented by cancer cells to the immune system and activate it.

Moreover, we isolated and characterized T-cells from donors that specifically recognize and react to this neoantigen. Through genetic techniques, we identified the T cell receptor in charge of the recognition and we have engineered other donor T-cells to enhance their ability to identify and destroy cancer cells carrying the KRAS G12V mutation, without attacking cells without this mutation.

We are developing and refining additional treatment modalities against KRAS G12V mutated cancers, including cancer vaccines, and unique bispecific antibodies. In addition, we have demonstrated the synergistic effect of combination therapy of chemotherapy and our engineered T-cells.

We aim to evaluate several treatment combinations against this neoantigen and refine the best option to pursue in clinical trials in novel mice models. Our work on KRAS G12V could impact the treatment of approximately 90,000 cancer patients each year who suffer from these aggressive cancer types, however, this research is not just about creating a new treatment for cancers with the KRAS G12V mutation. It's about paving the way for future therapies that can target other mutation derived neoantigens, offering new treatment options for many more patients.