Engineering T-Cell Specificity Genetically to Generate Anti-melanoma Reactivity

Melanoma tumors are known to harbor a high number of mutations leading to the expression of neo-antigens which can be recognized by the patient adaptive immune system. In this regard, immunotherapies involving adoptive cell transfer (ACT) of tumor-specific T-cells constitute a promising approach to treat melanoma. However, these cells do not always preexist in the patient or are difficult to isolate and/or expand. Thus, as the specificity of T-lymphocytes is determined by their T-cell receptor (TCR), it is possible to convert peripheral T-cells into cancer specific lymphocytes by transducing them to express a receptor that recognizes a defined tumor epitope. To this end, retroviral vectors can be used to efficiently transduce actively dividing cells such as proliferating T cells, while being relatively safe to the user. As we show herein, this approach is powerful and can be easily implemented, paving the way to the development of advanced research tools and potent clinical immunotherapeutic strategies.