Is Antigen Specificity the Key to Efficient Adoptive T-Cell Therapy?

Abstract

Adoptive transfer of T cells remains a promising approach in melanoma. Initial clinical trials performed with polyclonal tumor-infiltrating lymphocyte gave limited clinical results. Nonetheless, encouraging results have been reported in adjuvant setting (stage III melanoma), and when tumor-infiltrating lymphocytes were associated with lymphodepleting regimens. Specificity of adoptive cell therapy has been achieved with the infusion of antigen specific cytotoxic T-lymphocyte clones, associated with some clinical responses. Antigen specificity can also be obtained by the allogeneic transfer of high-avidity T-cell receptors into autologous T cells. We propose an alternative strategy based on the selection of antigen-specific T cells with magnetic beads coated with HLA–peptide multimers. Future improvements of adoptive melanoma immunotherapy may be achieved by its association with other therapeutic strategies such as targeted therapy against signaling pathways.

KEYWORDS::

• adoptive transfer
• antigen
• HLA
• melanoma
• peptide
• T-cell sorting

Acknowledgements

The authors would like to thank members of their laboratories for the accomplished work in the field of melanoma immunotherapy.

Financial & competing interests disclosure

This work was supported by grants from the Ligue Nationale contre le Cancer, INSERM, ENACT network number 503306, the Association pour la Recherche contre le Cancer No. 1074 and the Centre d‘Investigation Clinique de Biothérapie (Inserm 0503). The authors have 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 was supported by grants from the Ligue Nationale contre le Cancer, INSERM, ENACT network number 503306, the Association pour la Recherche contre le Cancer No. 1074 and the Centre d‘Investigation Clinique de Biothérapie (Inserm 0503). The authors have 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.