Improved Anti-Tumor Activity Demonstrated by the Combination of NKX019 and a CD20-directed Monoclonal Antibody in Preclinical Models
Pulsed Stimulation of NK Cells Derived from Peripheral Blood of Healthy Donors Induces Billion-Fold Expansion, Enabling Commercial-Scale Production of NK Cell Therapy from a Selected Single Donor
SOUTH SAN FRANCISCO, Calif., Nov. 07, 2022 (GLOBE NEWSWIRE) — Nkarta, Inc. (NASDAQ:NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, today announced the presentation of two preclinical data abstracts focused on its natural killer cell pipeline and proprietary manufacturing technology at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting and Pre-Conference Programs.
“Our presentations at this year’s SITC meeting illustrate the inherent power and potential of donor-derived NK cells,” said James Trager, PhD, Chief Scientific Officer of Nkarta. “Nkarta’s research team has shown that our manufacturing platform technology can expand NK cells by well over a billion-fold, while maintaining their integrity and potency. These findings could prospectively allow us to derive our CAR NK products from a very limited set of stringently selected donors. In a second study, the team has also further built on the considerable potency of our CD19-directed CAR NK candidate, NKX019.”
SITC 2022 abstracts will be available on the SITC website, https://www.sitcancer.org/2022/abstracts/abstract-titles-publications.
Nkarta’s posters will be available for download at https://www.nkartatx.com/publications/ after 9:00 a.m. ET on November 10, 2022.
Title: Large-scale expansion and engineering of human NK cells sourced from peripheral blood versus umbilical cord blood
Abstract Number: 381
Poster Presentation Date and Time: November 10, 2022, 9:00 a.m. – 9:00 p.m. ET
This study illustrates a remarkable >250-billion fold expansion of NK cells derived from peripheral blood using Nkarta’s proprietary NKSTIM cell line. NK cells maintained their potency, and showed no signs of chromosomal aberrations over an extended period of expansion. Both the expansion capacity and potency of NK cells derived from adult donors compared favorably to those from cord blood. Phenotypic analysis of expanded cells demonstrated the selective expansion or differentiation of in vivo educated NK cells. These cells could be identified and isolated from pre-expansion NK cells, and demonstrated superior expansion and native activity. These findings point the way toward selection of donors or of a specific cell population with optimal potential for expansion and potency based on straightforward phenotypic profiling.
Title: NKX019, an Off-the-Shelf CD19 CAR-NK Cell, mediates improved anti-tumor activity and persistence in combination with CD20-directed therapeutic mAbs
Abstract Number: 902
Poster Presentation Date and Time: November 11, 2022, 9:00 a.m. – 8:30 p.m. ET
In this preclinical study, the CD19-directed CAR NK, NKX019, was combined with the widely used anti-CD20 monoclonal antibodies (mAb) rituximab or obinutuzumab. These antibodies mediate both direct cell killing of CD20+ B cell malignancies, and can also mediate the antibody-dependent cellular cytotoxicity (ADCC) activity of NK cells through their interaction with CD16. Both the CAR NK cells and the monoclonal antibodies showed high potency against cell lines and primary malignant cells. When NKX019 was used with either mAb, their combined potency was greater than that of the individual agents alone. The potency of these combinations could be attributed in part to NKX019 ADCC activity, as demonstrated using an ADCC-deficient variant of rituximab and by increased degranulation of NKX019 in the presence of obinutuzumab. Results of this study point to a potential to combine these agents clinically to improve product potency and tumor targeting.
