CD38KO NK cell therapy has the potential to maximize the efficacy of anti-CD38 against multiple myeloma
Amsterdam, The Netherlands, July 22, 2020 – Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company developing innovative cell therapeutics for life-threatening diseases, today announces publication of an article in Blood, Journal of the American Society of Hematology. The article describes the synergy of mbIL21 expanded NK cells (FC21-NK) modified with a CD38 gene knockout together with an anti-CD38 monoclonal antibody (mAb) for enhanced killing of multiple myeloma cells.
The publication describes the use of the CRISPR/Cas9 system to delete CD38 (CD38KO) in ex vivo expanded peripheral blood K-NK cells, with 82% knock out efficiency. These CD38KO K-NK cells were completely resistant to anti-CD38 antibody-induced fratricide. In addition, as compared to wild type NK cells, the CD38KO K-NK cells showed superior persistence in immune deficient mice pre-treated with anti-CD38 antibody, and enhanced ADCC activity against CD38-expressing multiple myeloma cell lines and primary multiple myeloma cells. Additionally, analysis demonstrated that CD38KO K-NK cells have unique metabolic reprogramming with higher mitochondrial respiratory capacity, important in a hypoxic tumor micro-environment. Taken together, these findings provide proof-of-concept that adoptive immunotherapy using ex vivo expanded CD38KO K-NK cells has the potential to boost anti-CD38 antibody activity in multiple myeloma.
Dean Lee, MD, PhD, co-author of the article, Director of the Cellular Therapy and Cancer Immunology Program at Nationwide Children’s Hospital and The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard Solove Research Institute commented, “This work was a great opportunity to collaborate with Gabriel Ghiaur, MD, PhD, co-author of the article and Assistant Professor of Oncology at The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University. By combining the CRISPR/Cas9 technology with the FC21-NK cell platform we were able to produce and test an engineered NK cell therapeutic to address a recognized hurdle in immunotherapy of multiple myeloma. The ease and efficiency of this approach increases its potential to be translated to the clinic.”
Robert Friesen, chief scientific officer of Kiadis commented, “We are excited to see the published results of this scientific study, the proof-of-concept that targeted knockout of CD38 in highly stimulated NK cells can be synergistically applied to antibody treatments for the potential benefit of patients with multiple myeloma.”
Arthur Lahr, chief executive officer of Kiadis, added “This publication demonstrates that CD38KO K-NK cells are resistant to killing by anti-CD38 antibodies, and demonstrates how CD38KO K-NK cells improve potency of anti-CD38 antibodies. This data drove Sanofi’s excitement to license KNK004 for combination with Sarclisa®, to provide better treatment options for multiple myeloma patients. This data showcases the scientific rationale underpinning the collaboration with Sanofi, and should enhance the understanding of the potential of this combination.”