On August 29, 2022 ONK Therapeutics, an innovative company dedicated to developing optimally engineered natural killer (NK) cell therapies to cure patients with cancer, reported the first in-vivo data for ONKT102, a fully human, optimized affinity CD38 CAR-NK cell therapy (Press release, ONK Therapeutics, AUG 29, 2022, View Source [SID1234618722]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The positive data, presented in a poster at the International Myeloma Society late on Friday 26 August by ONK Therapeutics CSO Prof. Michael O’Dwyer showed potent anti-tumor activity for ONKT102 in-vitro and in-vivo in a CD38 positive MM.1S-LUC tumor model of multiple myeloma.
ONK Therapeutics is developing a pipeline of off-the-shelf, optimally engineered natural killer (NK) cell therapies expressing a chimeric antigen receptor (CAR), further modified to enhance tumor homing, persistence and metabolism, and to overcome exhaustion in the tumor microenvironment. Currently it has four programs in pre-clinical development across hematological malignancies and solid tumors. ONKT102 is the company’s most advanced program, and is being advanced towards clinical development as a potential treatment for patients with relapsed or refractory multiple myeloma (MM).
CD38 is an established immunotherapeutic target in MM. In this study, expanded cord blood (CB) derived NK cells first underwent CRISPR gene editing to knock out CD38 to prevent fratricide, following which they were genetically modified to express the optimized affinity CD38 CAR, using Tc Buster, a non-viral transposon approach developed by BioTechne. The anti-tumor efficacy of the optimized CD38 CAR-NK cells was then evaluated in NOD scid gamma (NSG) mice inoculated with MM.1S-LUC cells. Mice underwent weekly bioluminescient imaging to monitor tumor burden. The results showed that CD38 CAR-NK cells significantly reduced tumor burden and improved survival versus control CB NK cells and vehicle control.
Prof. Michael O’Dwyer, founder and CSO at ONK Therapeutics said, "These results suggest that non-virally engineered, optimized affinity CD38 CAR-NK CD38 KO cells have potent anti-tumor activity in-vitro and in-vivo in a CD38 positive tumor model.
"We are encouraged by these data and future work at ONK Therapeutics aims to optimize the dose and schedule, confirm the favorable safety profile and potential beneficial immune modulatory effects of our approach, as well as the added benefit of gene-editing with CRISPR/Cas9 to knock out CISH to enhance persistence."