Adoptive immunotherapy against sarcomas

Abstract

Introduction: Conventional treatments reached an unsatisfactory therapeutic plateau in the treatment of advanced unresectable bone and soft tissue sarcomas that remain an unsolved medical need. Several evidences support the concept that adoptive immunotherapy may effectively integrate within the complex and multidisciplinary treatment of sarcomas.

Areas covered: In this work we reviewed adoptive immunotherapy strategies that have been explored in sarcoma settings, with specific focus on issues related to their clinic transferability. We schematically divided approaches based on T lymphocytes specific for MHC-restricted tumor-associated antigens or relying on MHC-independent immune effectors such as natural killer (NK), cytokine-induced killer (CIK) or γδ T cells.

Expert opinion: Preclinical findings and initial clinical reports showed the potentialities and drawbacks of different adoptive immunotherapy strategies. The expansion of tumor infiltrating lymphocytes is difficult to be reproduced outside melanoma. Genetically redirected T cells appear to be a promising option and initial reports are encouraging against patients with sarcomas. Adoptive immunotherapy with MHC-unrestricted effectors such as NK, CIK or γδ T cells has recently shown great preclinical potential in sarcoma setting and biologic features that may favor clinical transferability. Combination of different immunotherapy approaches and integration with conventional treatments appear to be key issues for successful designing of next clinical trials.

Keywords:

• adoptive immunotherapy
• cytokine-induced killer cells
• natural killer cells
• sarcomas

Acknowledgement

G Mesiano and V Leuci contributed equally to this work.

Declaration of interest

This work was supported in part by grants from ‘Associazione Italiana Ricerca sul Cancro, AIRC I.G. grant. N. 11515, ‘Associazione Italiana Ricerca sul Cancro-AIRC 5X1000; Ricerca Finalizzata -Giovani Ricercatori (GR-2011-02349197), Fondo Ricerca Locale 2013. V Leuci is supported by Fondazione Umberto Veronesi. G Mesiano is supported by Associazione Italiana per la Ricerca sul Cancro (AIRC). Y Pignochino and S Capallero are sponsored in part by MIUR (University of Turin). 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. This manuscript, including figures, is original and has not been published before and is not currently being considered for publication elsewhere.

Notes

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