Precomplexing NK cells with Innate Cell Engagers (ICE® molecules) results in a CAR-like NK cell product, whose magnitude and specificity of antibody-dependent cellular cytotoxicity (ADCC) remain unaffected after one freeze-thaw cycle
Activity after cryopreservation is an important prerequisite for the development of off-the-shelf NK cell therapeutics and CD16A-specific ICE® molecules that are precomplexed with NK cells show promise for further development
Heidelberg, Germany, February 9, 2021 – Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, today announced the publication of pre-clinical data demonstrating the cytotoxic potency and efficacy of NK cells precomplexed with ICE® molecules after one cycle of cryopreservation. This is an important prerequisite for the development of off-the-shelf products which may allow accessibility to the novel treatment option for patients in need.
The data show experimental results of NK cells precomplexed with three bispecific, tetravalent ICE® molecules targeting the validated tumor target EpCAM and one of the NK cell-activating receptors CD16A, NKG2D or NKp46. NK cells precomplexed to the EpCAM/CD16A ICE® molecule demonstrated superior cytotoxicity against EpCAM-positive tumor cells in comparison to complexes with EpCAM/NKG2D and EpCAM/NKp46 ICE® formats. This effect may potentially be driven by a stronger NK cell activation through CD16A as compared to NKG2D or NKp46. After one cycle of cryopreservation, this effect continued – notably, NK cells precomplexed with all three ICE® constructs retained their cytotoxicity after freezing and thawing.
“The finding that NK cells precomplexed with the EpCAM/CD16A ICE® molecule show superior cytotoxic activity that remained unaffected after freezing and thawing, when compared to combinations with ICE® molecules targeting NKG2D or NKp46 after similar freezing and thawing is exciting. This finding holds promise for the future development of off-the-shelf precomplexed ICE® molecules targeting NK cells through CD16A,” said Arndt Schottelius, Chief Scientific Officer of Affimed.
“The high cytotoxicity of NK cells precomplexed with ICE® molecules after cryopreservation is important in the context of the exciting data that were generated in an ongoing investigator initiated phase 1-2 study of cord blood derived NK cells precomplexed with AFM13 in patients with CD30-positive lymphomas, where, at the highest dose level, a 100% objective response rate was seen,” added Andreas Harstrick, Chief Medical Officer of Affimed.
The manuscript has been published in a special issue on Antibodies for Effector Cell Redirection in the journal Antibodies and is available here: https://www.mdpi.com/2073-4468/11/1/12#