INSERM 892, 9, quai Moncousu, 44093 Nantes cedex
Amplification of antitumoral responses in patients with cancer and restoration of viral immunity in immunocompromized patients are the two main applications for adoptive transfer of specific T lymphocytes. However, these protocols are unlikely to be widely applicable in clinical practice. First, there is insufficient knowledge concerning the composition of the clinically relevant T cell repertoire. Second, such protocols are hampered by the discordance between the emergency of treatment and the long length of time necessary to enrich and expand specific T cells, for example in the case of viral complications. Moreover, their current restricted application to small groups of patients limits the information that can be gained from these studies. Such approaches are associated with many complex elements, including technical difficulties associated with specific T cell selection and amplification, and uncertainty in terms of the clinical relevance of the targeted antigens. Nevertheless, given the well known effects of T cells in bone marrow transplantation, it remains clear that if the huge potential of the infused T cells could be controlled, this would open the way for considerable therapeutic progress. If adoptive transfer of T lymphocytes is to become widely applicable, the design of protocols with a reduced number of issues addressed and an increased number of patients is necessary. With this in mind, several groups, including ourselves, are currently working on strategies that rely on gene transfer in order to redirect T-cell specificity against antigens such as CD19 or CD33, or to arm specific T cells with a receptor that would enable them to mediate ADCC. The latter approach will require solving the safety issues associated with gene transfer and demonstration of efficiency. Nevertheless, if successful, the ADCC strategy would enable the treatment of a large number of patients using the same type of T cell effectors.