On April 17, 2023 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported the presentation of two preclinical data abstracts focused on its natural killer cell pipeline and proprietary manufacturing technology at the 2023 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Nkarta, APR 17, 2023, View Source [SID1234630166]).

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"Our AACR (Free AACR Whitepaper) presentations demonstrate the potential to combine our engineered, donor-derived NK cell therapies with monoclonal antibodies to extend and enhance the potency of both modalities," said James Trager, PhD, Chief Scientific Officer of Nkarta. "We have shown that our products maintain high levels of CD16 and that the binding of appropriate monoclonal antibodies to CD16 can expand the targeting and potency of CAR NK cells. Specifically, we’ve shown that NKX101, our clinical candidate engineered with an NKG2D-based CAR, can be combined with cetuximab to enhance activity towards EGFR-expressing tumor cells. We’ve also shown that CRISPR-mediated knockout of ADAM17, a suppressor of CD16 activity, can be used to further elevate ADCC, and to help maintain NK cell potency. These findings will be critical groundwork for developing successful therapeutic combinations that include treatment with CAR NK cells, particularly in solid tumor settings."

Nkarta’s 2023 AACR (Free AACR Whitepaper) posters will be available for download shortly after their scheduled presentation at View Source

ADAM17 knockout NK or CAR NK cells augment antibody dependent cellular cytotoxicity (ADCC) and anti-tumor activity
Abstract Number 890
April 16, 2023, 1:30 p.m. – 5:00 p.m. ET

In this study, ADAM17 KO CAR NK cells demonstrate improved ADCC and ADAM17 KO can enhance in vivo anti-tumor activity of CISH/CBLB KO CD70 CAR NK cells in relevant tumor models. ADAM17 KO NK cells maintain dramatically higher surface expression of CD16a and CD62L than control NK cells. ADAM17 KO CD19 CAR NK cells demonstrate higher cytotoxicity compared to control NK cells against Raji tumor cells in the presence of rituximab (anti-CD20). Similarly, ADAM17 KO CD70 CAR NK cells also possess enhanced cytotoxicity against 786-O tumor cells in the presence of the anti-EGFR antibody, cetuximab. Furthermore, ADAM17/CISH/CBLB triple KO CD70 CAR NK cells have improved antitumor efficacy in vivo in an HL60 AML xenograft model. These data support the further exploration of ADAM17 KO CAR NK cells for clinical application and to improve the efficacy of therapeutic antibodies in combination with the adoptive transfer of engineered NK cells.

Combination of anti-EGFR antibody cetuximab with NKX101, an allogeneic NKG2D-L targeting NK cell therapy, enhances potency and in vitro cytotoxicity against solid tumors
Abstract Number 3183
April 17, 2023, 1:30 p.m. – 5:00 p.m. ET

This study demonstrates that cetuximab, a human IgG1 antibody targeting epidermal growth factor receptor (EGFR) approved for the treatment of colorectal and head and neck cancers, increases the anti-tumor effect of NKX101 in a dose-dependent manner. Assessment of the interaction between NKX101 and cetuximab in vitro revealed that the two agents can combine to kill cancer cells in a synergistic manner. Blocking CD16 on NKX101 cells with a neutralizing antibody significantly decreases the potency of the combination, suggesting that the improvement in potency observed is a direct result of CD16-mediated ADCC activity. It was also demonstrated that common CD16 polymorphisms do not influence NKX101 ADCC activity. This study shows that the combination of an engineered allogeneic NK cell therapy, NKX101, with cetuximab leads to an increase in the specific killing of cancer cells in vitro and supports further investigation into this combination for the treatment of solid tumors.