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Lytic activity against primary AML cells is stimulated in vitro by an autologous whole cell vaccine expressing IL-2 and CD80

  • Nicola Hardwick
  • Lucas Chan
  • Wendy Ingram
  • Ghulam Mufti
  • Farzin FarzanehEmail author
Original Article

Abstract

Despite being of the myeloid lineage, acute myeloid leukaemia (AML) blasts are of low immunogenicity, probably because they lack the costimulatory molecule CD80 and secrete immunosuppressive factors. We have previously shown that in vitro stimulation of autologous peripheral blood mononuclear cells (PBMCs) with primary AML cells modified to express CD80 and IL-2 promotes proliferation, secretion of Th1 cytokines and expansion of activated CD8+ T cells. In this study, we show that allogeneic effector cells (from a healthy donor or AML patients) when stimulated with IL-2/CD80 modified AML blasts were able to induce the lysis of unmodified AML blasts. Effector cells stimulated with IL-2/CD80AML blasts had higher lytic activity than cells stimulated with AML cells expressing CD80 or IL-2 alone. Similarly, AML patient PBMCs primed with autologous IL-2/CD80 AML cells had a higher frequency of IFN-γ secreting cells and show cytotoxicity against autologous, unmodified blasts. Crucially, the response appears to be leukaemia specific, since stimulated patient PBMCs show higher frequencies of IFN-γ secreting effector cells in response to AML blasts than to remission bone marrow cells from the same patients. Although studied in a small number of heterogeneous patient samples, the data are encouraging and support the continuing development of vaccination for poor prognosis AML patients with autologous cells genetically modified to express IL-2/CD80.

Keywords

Acute myeloid leukaemia Cellular therapy Gene therapy CD80 IL-2 

Notes

Acknowledgments

We are grateful to Dr Linda Barber for critical feedback on this manuscript. This work was funded by The Leukaemia Research Fund and The Elimination of Leukaemia Fund. The authors also acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Nicola Hardwick
    • 1
  • Lucas Chan
    • 1
  • Wendy Ingram
    • 1
  • Ghulam Mufti
    • 1
  • Farzin Farzaneh
    • 1
    Email author
  1. 1.Department of Haematological Medicine, King’s College LondonThe Rayne InstituteLondonUK

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