NK Cells in the treatment of Multiple Myeloma
- Slides: 8
NK Cells in the treatment of Multiple Myeloma Michael O’Dwyer MD Professor of Hematology, National University of Ireland, Galway
Disclosures • CSO ONK Therapeutics (Ownership and employment)
The balance between activating and inhibitory inputs determines NK killing of target cells
NK cells are dysfunctional in Myeloma CONFIDENTIAL Adapted from Fionda et al, Cancer Treatment Reviews 2018
Treatments employing endogeneous NK cells
Engineering NK cells to optimize their function Adapted from Sarkar S, O’Ceallaigh C, O’Dwyer M. Cell and Gene Therapy Insights 2019
CAR-NK. v. CAR-T Cell source Mode of action Engineering Complete response rate (CD 19 B cell malignancies) Toxicity Profile Dosing frequency Persistence Setting of administration Cost/dose Existing CAR-T cells Engineered NK cells Autologous – Leukapheresis from patients with ex-vivo engineering. Complicated process, takes weeks Allogeneic – Frozen, off-theshelf engineered cells. Immediately available Antigen or CAR-dependent Innate killing independent of antigen and HLA Easy to engineer with viral and nonviral approaches Historically more challenging to engineer, but progress ++ 7— 90% CR 8/11 CR* High rates of severe CRS (~30%) and severe neurotoxicity (45%) No observed CRS or neurotoxicity Single dose Potential for multi-dosing Long term, > 6 months common Short term without IL-15, CISH KO etc. In patient with ICU available Outpatient $$$$ $$ *Liu E, et al. N Engl J Med. 2020 Feb 6; 382(6).
The Future: multi-targeted CAR-NK approach for Myeloma BCMA, SLAMF 7 or