4.3 Article

Cytotoxic T Cells Activated by Self-differentiated Monocyte- derived Dendritic Cells Against Multiple Myeloma Cells

Journal

ANTICANCER RESEARCH
Volume 42, Issue 4, Pages 1785-1799

Publisher

INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.15655

Keywords

Multiple myeloma; adoptive T cell therapy; dendritic cells; cytotoxic T cells; B cell maturation antigen

Categories

Funding

  1. TRF-International Research Network (TRF-IRN) [IRN58W0001]
  2. Center of Excellence on Medical Biotechnology (CEMB), S&T Postgraduate Education and Research Development Office (PERDO), Office of Higher Education Commission (OHEC), Thailand [CB61-006-01]
  3. Siriraj Research Fund of the Faculty of Medicine Siriraj Hospital, Mahidol University [R016034008]
  4. Mahidol University [BRF1-029/2565]
  5. TRF-IRN Scholarship [IRN5801PHDW05]
  6. Siriraj Graduate Scholarship
  7. National Research Council of Thailand (NRCT) [N41A640177]
  8. Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation [RGNS 63068]
  9. TRF Grant for New Researcher [TRG5780173]
  10. Siriraj Chalermprakiat Grant

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This study evaluated the effectiveness of self differentiated monocyte-derived dendritic cells expressing BCMA (SD-DC-BCMA) in activating T cells to kill multiple myeloma cells. T cells activated by SD-DC-BCMA showed dose-dependent cytotoxicity against BCMA-expressing MM cells and produced high levels of IFN-gamma.
Background/Aim: B cell maturation antigen (BCMA) is an ideal target for adoptive T cell therapy of multiple myeloma (MM). In this study, we evaluated self differentiated monocyte-derived dendritic cells expressing BCMA (SD-DC-BCMA) to activate T cells for killing MM cells. Materials and Methods: Lentivirus-modified SD-DCBCMA harboring tri-cistronic cDNAs encoding granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin4 (IL-4), and BCMA was generated. Cytotoxicity of T cells activated by SD-DC-BCMA against MM cells was evaluated. Results: T cells activated by SD-DC-BCMA exhibited a dose dependent cytotoxicity against BCMA-expressing MM cells and produced high IFN-gamma levels, compared to inactivated T cells or control T cells. A significantly higher killing ability of T cells activated by SD-DC-BCMA was further demonstrated in BCMA-overexpressing cells when compared with BCMAnegative cells. Conclusion: The potency of SD-DC-BCMA to activate T cells for antigen-specific cancer killing provides a framework for therapeutic application of adoptive T cell therapy in MM.

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