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Human CD80/IL2 lentivirus transduced acute myeloid leukaemia cells enhance cytolytic activity in vitro in spite of an increase in regulatory CD4+ T cells in a subset of cultures

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Abstract

Immunotherapeutic strategies are increasingly being explored as a method of enhancing anti-tumour immune responses in patients with acute myeloid leukaemia (AML). Regulatory CD4+ T cells (Tregs) suppress effector T and natural killer (NK) cells and therefore pose a potential challenge to the efficacy of immunotherapy. AML cells transduced with a lentivirus expressing CD80 (B7.1) and IL2 (LV-CD80/IL2) are capable of stimulating T and NK cell cytotoxicity in vitro. This study examines the effect of CD80/IL2 modified AML cells on Treg number and function. We report a significant increase in the number of CD8+ T cells (P = 0.046) CD3−CD56+ NK cells (P = 0.028) and CD3+CD4+CD25highFoxp3+ Tregs (P = 0.043) following stimulation for 7 days with allogeneic LV-CD80/IL2 AMLs. In contrast, autologous LV-CD80/IL2 AML cell cultures provide a weaker stimulation with a lower number of CD8+ T cells (P = 0.011) and no change in NK cell or Treg numbers. However, an increase in cytotoxic CD8+ T cells and NK cells are detected following both allogeneic and autologous LV-CD80/IL2 stimulation as demonstrated by an increase in IFN-γ and CD107a expression. Despite the presence of increased numbers of Tregs with suppressive activity in a subset of cultures, increased lysis of unmodified AMLs was still achieved following allogeneic (day 0, 2.2%; day 7, 20.4%) and more importantly, autologous LV-CD80/IL2 culture in which AML patients had recently received intensive chemotherapy (day 0, 0%; day 7, 16%). Vaccination with LV-CD80/IL2 therefore provides a potential strategy to enhance anti-leukaemia immune responses without a concomitant stimulation of Treg-mediated inhibition of cytotoxic immunological responses.

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Acknowledgments

W. Ingram was supported by the Leukaemia Research Fund and the Biomedical Research Centre, King’s College London. S. Kordasti was supported by Joint Research Committee of King’s College Hospital and King’s College London.

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  1. Department of Haematological Medicine, King’s College London, Rayne Institute, 123 Coldharbour Lane, London, SE5 9NU, UK

    Wendy Ingram, Shahram Kordasti, Lucas Chan, Linda D. Barber, Gee J. Tye, Nicola Hardwick, Ghulam J. Mufti & Farzin Farzaneh

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  1. Wendy Ingram
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Correspondence to Ghulam J. Mufti.

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Ingram, W., Kordasti, S., Chan, L. et al. Human CD80/IL2 lentivirus transduced acute myeloid leukaemia cells enhance cytolytic activity in vitro in spite of an increase in regulatory CD4+ T cells in a subset of cultures. Cancer Immunol Immunother 58, 1679–1690 (2009). https://doi.org/10.1007/s00262-009-0679-6

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