Therapy with cultured T cells: principles revisited

Abstract

In animals and in humans, T-cell therapy can cure advanced disseminated leukemia that would otherwise be fatal. The therapeutic effect of immune T cells is quantitative. As the dose of effector T cells is increased, survival is proportionately increased. Therefore, effective T-cell therapy is predicated on the ability to procure large numbers of immune effector T cells. By using cultured T cells, the number of immune T cells can be increased in vivo substantially above the level achievable by vaccination. The survival of cultured T cells in vivo is dependent upon both the culture conditions used and the therapeutic regimens employed. Under appropriate conditions, cultured T cells can proliferate in vivo in response to stimulation by antigen, distribute widely and survive long term to provide effector function and immunologic memory. Given that T cells recognize peptides, the need for immunization with tumor can be circumvented by immunization with peptide. Peptide-specific T cells and the progeny of single T-cell clones can provide the necessary cellular functions to eradicate disseminated murine leukemia. The ability of cloned T cells to similarly provide substantial measurable immunity in humans has been validated in clinical trials. By priming with peptides and by using established culture conditions, T-cell therapy can now be directed against virtually any antigen within the host T-cell repertoire. The major remaining question to be answered is which proteins and which peptides are the most suitable targets for T-cell therapy trials.