Grant: Project Grant

Immunotherapy has proven to be an invaluable tool for the treatment of cancer. However, due to patient and tumour heterogeneity, certain cancers remain unresponsive to immunotherapy. Therefore, there is a critical need to develop efficient and broadly applicable therapeutic strategies, and to better understand what factors govern responsiveness vs. unresponsiveness to these therapies. Cell-based adoptive therapies with engineered T cells are efficient in treating blood cancers, but their efficacy against solid tumours like lung cancer remains limited. In addition, due to intrinsic T cell properties, only the patient's own T cells can be used to prevent the risk of bystander damage to healthy cells. For this reason, T cell-based adoptive cell therapies remain highly personalized. Invariant Natural Killer T (iNKT) cells are special T cells that contribute to tumour rejection through different mechanisms, including the direct killing of tumour cells. iNKT cells can be safely transferred between unrelated individuals. This unique property led to ongoing clinical trials for various cancers, including solid tumours. Although promising, the response rate and efficacy of iNKT cell-based immunotherapies remain suboptimal, possibly due to the functional heterogeneity of iNKT cells. Our research has identified a subset of highly cytotoxic iNKT cells with superior tumour-killing capabilities. These cells are found within lung tumours from non-small cell lung cancer patients, and in the blood of healthy donors. Our objective is to assess their ability to kill tumour cells in various preclinical settings. This work lays the foundation for an innovative and broadly applicable adoptive cell therapy to treat lung cancer.