Effective Adoptive T-Cell Therapy for Cancer in the Absence of Host Lymphodepletion

Abstract

Evaluation of: Ly LV, Sluijter M, Versluis M et al.: Peptide vaccination after T-cell transfer causes massive clonal expansion, tumor eradication and manageable cytokine storm. Cancer Res. 70(21), 8339-46 (2010). Adoptive T-cell transfer (ACT) to treat cancer, autoimmunity and infectious disease holds great promise. In the cancer field, current dogma suggests that achieving a high frequency of circulating, transferred T cells is critical for therapeutic success. Achieving this high level of T-cell engraftment currently requires preconditioning of the patient. In effect, this means the eradication of the patient's own immune system, thereby creating 'space' for the adoptively transferred T cells to populate in the absence of host-cell competition. While different forms of preconditioning are employed, each carries a significant level of toxicity itself. In the paper being evaluated, Ly et al. demonstrate that the combination of ACT with vaccination using long peptides, a Toll-like receptor-7 ligand and cytokine support in the form of IL-2 can drive the expansion of adoptively transferred antigen-specific T cells in the absence of preconditioning regimens. This paper infers that reduced intensity regimens may be suitable for ACT clinical protocols.