Could CAR-NK Cells Using Cord Blood Offer a Treatment for Multiple Myeloma?

For several years, investigators have examined the potential for allogenic natural killer (NK) cells as an alternative for “off-the-shelf” chimeric antigen receptor (CAR) treatments. The upside is less time to treatment for patients, but the downside in targeting CD38 could be an increased risk of off-target toxicity.

Recently, at the International Myeloma Society (IMS) meeting in Los Angeles August 25-27, results for a new concept were presented from ONK Therapeutics, a biotech based in Galway, Ireland, and San Diego. Building on prior work, investigators started with cord blood to develop optimized affinity CD38 CAR-NK cells for the treatment of multiple myeloma (MM).

Cord blood derived NK cells, they said in their poster presentation, “have previously shown potential as immunotherapy for MM.” The presentation by ONK Founder and Chief Scientific Officer Michael O’Dwyer, MD, also incorporated gene editing with CRISPR/Cas9 to knock out CD38, “to overcome fratricide as well as potentially enhance persistence.”

In statement, ONK Therapeutics said that the presentation of in vivo data for ONKT102, the experimental treatment, shows “potent anti-tumor activity.”

For the study presented at IMS, expanded cord blood derived underwent the CRISPR gene editing process and were then modified to express the optimized affinity CD38 CAR, using a cell transfer approach developed by BioTechne. The efficacy of this method was evaluated in modified mice that were inoculated with MM cells. The mice then received weekly imaging to monitor their tumor burden, and results showed that the CD38 CAR-NK cells significantly reduced the tumor burden—and improved survival—compared control cells as well as vehicle control.

“These results suggest that non-virally engineered, optimized affinity CD38 CAR-NK CD38 [knockout] cells have potent anti-tumor activity in-vitro and in-vivo in a CD38 positive tumor model,” O’Dwyer said in a statement.

“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.”

Reference

Brophy S, Kirkham McCarthy L, Köylijärvi M, et al. CB derived, optimized affinity CD38 CAR-NK cells with CD38 KO show promising in-vivo activity in a multiple myeloma model. Presented at: 19th International Myeloma Society; Los Angeles, California, August 25-27, 2022. Abstract P-018.