Multiparameter monitoring for optimal T-cell adoptive therapy

Abstract

Adoptive transfer of ex vivo -expanded antigen-specific T cells is a promising therapeutic approach for the treatment of cancer and infectious diseases. Clinical studies have proven the feasibility and potency of this procedure but several limitations need to be overcome before this form of immunotherapy reach its full potential. For instance, the efficacy of the transferred cells is often impeded by terminal effector differentiation and exhaustion acquired during in vitro expansion. This would notably explain the lack of further in vivo proliferation and persistence in many trials. However, the factors that induce T-cell differentiation and functional impairment in culture remain poorly defined. Using the model antigen HA-1, we determined that phenotypic and functional features indicating T-cell exhaustion/dysfunction may not be detected simultaneously and depend on the method of expansion as well as the antigenic repertoire stimulated. Thus, our study has defined critical parameters to monitor in order to optimally differentiate and expand antigen-specific T cells in culture prior to adoptive transfer.