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), 8339–8346 (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.

KEYWORDS::

• adoptive transfer
• lymphodepletion
• T cell
• Toll-like receptor
• toxicity
• vaccination

Financial & competing interests disclosure

This work has been supported by grants from Cancer Research UK, Kay Kendall Leukaemia Fund, European Union Framework 6 Grant ‘ATTACK‘ and Framework 7 Grant ‘ATTRACT‘ and the University of Manchester. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work has been supported by grants from Cancer Research UK, Kay Kendall Leukaemia Fund, European Union Framework 6 Grant ‘ATTACK‘ and Framework 7 Grant ‘ATTRACT‘ and the University of Manchester. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.