A new method for modified NK cells

DRESDEN, Germany—GEMoaB Monoclonals GmbH has reported that an article on their preclinical proof-of-concept data on UniCAR-modified off-the-shelf natural killer (NK) cells targeting GD2-expressing tumors has been published in Nature Scientific Reports. The data generated by researchers at the Helmholtz-Center Dresden-Rossendorf (HZDR) provide further evidence on the unique flexibility of GEMoaB´s proprietary UniCAR platform.

CAR-T cell therapy holds great promise for treating a wide range of malignancies, but the CAR-T approach faces multiple challenges — including the risk of acute and long-term toxicities, a lack of suitable targets, insufficient engraftment, and persistence, especially in solid tumors. And the currently available commercial CAR-T products can only be derived from individual patients, which adds significant complexity and cost to the autologous manufacturing process.

GEMoaB’s UniCAR, a rapidly switchable universal CAR platform, promises an improved therapeutic window and increased efficacy and safety over conventional CAR-T therapies in hematological malignancies and solid tumors. As soluble adaptors called targeting modules (TMs) are used to provide the antigen-specificity to activate UniCAR gene-modified T-cells (UniCAR-T), the manufacturing process is significantly simplified by the ability to use the same UniCAR-T effector cell against multiple antigens and tumor types.

“We are very pleased that our co-founder Prof. Michael Bachmann and researchers of the HZDR could demonstrate that GEMoaB’s highly flexible UniCAR system can be readily applied to continuously expanding off-the-shelf NK cells, which in combination with GD2-specific TMs efficiently target and lyse GD2-expressing tumor cells such as neuroblastoma and melanoma,” said Prof. Gerhard Ehninger, co-founder and chief medical officer of GEMoaB. “UniCAR-NK cells could represent an additional universal and modular off-the-shelf platform that would allow the use of TMs against multiple antigen targets for an effective and safe therapy of cancer.”

NK cells that are genetically engineered to express a CAR (CAR-NK) have recently emerged as promising candidates for effective cancer treatment. Off-the-shelf CAR-NK cells from an allogeneic source like umbilical cord blood can be safely administered without the need for full human leukocyte antigen (HLA) matching. This eliminates the need to produce a unique CAR product for each patient. And allogeneic CAR-NK cells have a proven track record of safety, since they are known to not cause cytokine release syndrome.

In the recent Nature Scientific Reports publication, researchers of the HZDR combined the advantages of the UniCAR approach with the off-the shelf capabilities of NK cells. The article provides proof-of-concept for a universal off-the-shelf cellular therapeutic based on UniCAR-modified NK-92 cells retargeted to GD2-expressing tumors by GD2-specific TMs. Redirected UniCAR-NK-92 cells induced specific and effective killing of GD2-expressing cells both in vitro and in vivo, associated with enhanced interferon-γ production.

“As we are progressing with our clinical development plans for UniCAR-T-CD123 in hematological malignancies and UniCAR-T-PSMA in solid tumors, we are developing a deep pipeline of TMs directed against a wide variety of blood and solid tumor cancers. We believe that UniCAR-NK cells could further enhance the unique flexibility of our platform by combining the advantages of UniCAR with the safety and off-the-shelf capabilities of NK cells,” noted Dr. Armin Ehninger, chief scientific officer of GEMoaB.