Phase I Clinical Trial of ThINKK Adoptive Immunotherapy After Allogeneic Hematopoietic Transplantation in Children With Leukemia or Neuroblastoma
Summary
A first-in-class adoptive immunotherapy we called ThINKK, for Therapeutic Inducers of Natural Killer (NK) cell Killing, have been designed for use after hematopoietic stem cell transplantation (HSCT), where the proper stimulation of graft-derived NK cells has been shown to prevent relapse. ThINKK immunotherapy builds on our earlier research on NK cells and plasmacytoid dendritic cells (PDC) in cord blood and after HSCT. PDC are the sentinels of the immune system. Upon viral nucleic acids detection, PDC secrete a vast array of chemokines and cytokines that stimulate NK cells. PDC stimulation enhances NK cells killing of infected cells that express stress-induced molecules. Cancer cells also express stress-related molecules at their surface. However, NK cells do not receive PDC stimulation when fighting cancer. ThINKK therapy is designed to provide this necessary stimulation.
Timeline
- Start
- 2026-05-01
- Primary completion
- 2029-05-01
- Completion
- 2029-05-01
Publications
- Background Cordeau M, Belounis A, Lelaidier M, Cordeiro P, Sartelet H, Herblot S, Duval M. Efficient Killing of High Risk Neuroblastoma Using Natural Killer Cells Activated by Plasmacytoid Dendritic Cells. PLoS One. 2016 Oct 7;11(10):e0164401. doi: 10.1371/journal.pone.0164401. eCollection 2016.
- Background Belounis A, Ayoub M, Cordeiro P, Lemieux W, Teira P, Haddad E, Herblot S, Duval M. Patients' NK cell stimulation with activated plasmacytoid dendritic cells increases dinutuximab-induced neuroblastoma killing. Cancer Immunol Immunother. 2020 Sep;69(9):1767-1779. doi: 10.1007/s00262-020-02581-0. Epub 2020 Apr 27.
- Background Poirier N, Paquin V, Leclerc S, Lisi V, Marmolejo C, Affia H, Cordeiro P, Theoret Y, Haddad E, Andelfinger G, Lavallee VP, Duval M, Herblot S. Therapeutic Inducers of Natural Killer cell Killing (ThINKK): preclinical assessment of safety and efficacy in allogeneic hematopoietic stem cell transplant settings. J Immunother Cancer. 2024 May 15;12(5):e008435. doi: 10.1136/jitc-2023-008435.
- Background Diaz-Rodriguez Y, Cordeiro P, Belounis A, Herblot S, Duval M. In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells. Cancer Immunol Immunother. 2017 Oct;66(10):1307-1320. doi: 10.1007/s00262-017-2022-y. Epub 2017 May 29.
- Background Lelaidier M, Diaz-Rodriguez Y, Cordeau M, Cordeiro P, Haddad E, Herblot S, Duval M. TRAIL-mediated killing of acute lymphoblastic leukemia by plasmacytoid dendritic cell-activated natural killer cells. Oncotarget. 2015 Oct 6;6(30):29440-55. doi: 10.18632/oncotarget.4984.
- Background Charrier E, Cordeiro P, Brito RM, Mezziani S, Herblot S, Le Deist F, Duval M. Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children. Bone Marrow Transplant. 2013 Mar;48(3):376-82. doi: 10.1038/bmt.2012.176. Epub 2012 Oct 15.
- Background Charrier E, Cordeiro P, Brito RM, Harnois M, Mezziani S, Herblot S, Le Deist F, Duval M. Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy. Biol Blood Marrow Transplant. 2014 Oct;20(10):1501-7. doi: 10.1016/j.bbmt.2014.06.007. Epub 2014 Aug 14.