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531 AFM13-targeted blood and cord-blood-derived memory-like NK cells as therapy for CD30+ malignancies
  1. Lucila Kerbauy1,
  2. Nancy Marin2,
  3. Mecit Kaplan1,
  4. Pinaki Banerjee1,
  5. Melissa Berrien-Elliott2,
  6. Michelle Becker-Hapak2,
  7. Rafet Basar1,
  8. Mark Foster2,
  9. Luciana Garcia Melo3,
  10. Carly Neal2,
  11. Ethan McClain2,
  12. May Daher1,
  13. Ana Karen Nunez Cortes1,
  14. Sweta Desai2,
  15. Francesca Wei Inng Lim1,
  16. Mayela Carolina Mendt1,
  17. Timothy Schappe2,
  18. Li Li1,
  19. Hila Shaim1,
  20. Mayra Hernandez Sanabria1,
  21. Pamela Wong2,
  22. Enli Liu1,
  23. Sonny Ang1,
  24. Rong Cai1,
  25. Vandana Nandivada1,
  26. Vakul Mohanty1,
  27. Yifei Shen1,
  28. Natalia Baran1,
  29. Natalie Fowlkes1,
  30. Ken Chen1,
  31. Luis Muniz-Feliciano1,
  32. Joachim Koch4,
  33. Martin Treder5,
  34. Wolfgang Fischer4,
  35. Oswaldo Keith Okamoto6,
  36. Yago Nieto1,
  37. Richard Champlin1,
  38. Elizabeth Shpall1,
  39. Todd Fehniger2 and
  40. Katy Rezvani1
  1. 1The University of Texas MDACC, Houston, USA
  2. 2Washington University School of Medicine, St Louis, MO, USA
  3. 3The University of Texas MD, Houston, USA
  4. 4Affimed GmbH, Heidelberg, Germany
  5. 5Arjuna Therapeutics, Santiago de Compostela, Spain
  6. 6Hospital Israelita Albert Einstein, Sao Paulo, Brazil


Background Natural killer (NK) cells are a nascent cellular immunotherapy for hematologic malignancies. Target recognition of NK cell-resistant cancers remains a substantial barrier to broad application of NK cell therapy. One solution are bispecific engagers that trigger NK cells via an NK activating receptor when simultaneously engaging a tumor-specific antigen.

Methods Here, we investigated single NK cell responses stimulated by the tetravalent bispecific innate cell engager (ICE®) AFM13 that binds CD30 on leukemia/lymphoma targets and CD16A on several types of NK cells.

Results Multidimensional mass cytometry revealed heterogeneity within AFM13-directed conventional (c)NK cell responses, as well as consistent polyfunctional activation of mature terminally differentiated NK cells across donors. The source of NK cells also impacted the AFM13 response, with cNK cells from healthy donors exhibiting superior responses to those from Hodgkin lymphoma patients. IL-12, IL-15, and IL-18-induced memory-like NK cells from peripheral blood exhibited enhanced killing of CD30+ lymphoma targets directed by AFM13, compared to cNK cells. Cord-blood expanded NK cells that were pre-activated with IL-12, IL-15 and IL-18 also exhibited enhanced killing with AFM13 stimulation, via upregulation of signaling pathways related to NK cell effector function. These cells were stably pre-loaded with AFM13 enhancing responses to CD30+ lymphomas in vitro and in vivo in immunodeficient NSG mouse models.

Conclusions Collectively, these data identify promising combinations of AFM13 with cytokine-activated adult blood or cord blood NK cells against CD30+ hematologic malignancies, warranting clinical trials with these novel combinations.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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