Blocking CD38 using Daratumumab F(ab)2 to Protect Natural Killer Cells from Daratumumab-induced Apoptosis and Cell Death for the Treatment of Multiple Myeloma

This technology includes the method of blocking CD38 in expanded natural killer (NK) cell therapy in combination with daratumumab in patients with multiple myeloma. Our in vitro studies have already confirmed the addition of NK cells to myeloma cells that have been exposed to daratumumab enhances myeloma killing compared to single agent treatment. Studies exploring adoptive NK cell transfer after daratumumab treatment to bolster daratumumab-mediated killing of myeloma via ADCC could be limited by the fact that these transferred NK cells might be killed by the antibody before they could reach their antibody-bound tumor targets. To overcome this obstacle, we have explored blocking CD38 on the surface of NK cells with a daratumumab F(ab)2 fragment as a method to prevent daratumumab- induced apoptosis of NK cells. We have generated daratumumab F(ab)2 fragments using enzymatic cleavage of daratumumab and have confirmed these fragments bind to CD38 expressed on NK cells.