Antibody Recruiting Molecules (ARM™s) in Natural Killer (NK) Cell Combination Therapy
Natural Killer (NK) Cells are a type of immune effector cell that can recognize and destroy non-self targets and certain diseased cell. NK cells do not target specific protein epitopes like T cells of the adaptive immune system. Kleo’s ARMs are being used to redirect engineered NK cells localize at sites of specific disease cell targets for enhanced efficacy. ARMs can bind and redirect NK cells via saturated levels of IgG that coat the cells. For this combination therapy, the ARM is added ex vivo to saturate the surface of the NK cell before systemic administration.
Biohaven’s CD38-targeting ARM (KP1237) is being used in combination with autologous NK cells (and low-dose IL2) in a Phase 12 clinical trial for post-transplant multiple myeloma (MM) patients targeting CD38-positive MM/plasma cells..
CD38-ARM Advantages over CD38 Therapeutic Antibodies
- Do not cause NK Cell fratricide
- Do not stimulate CDC activity
- Show equivalent efficacy in ex vivo studies with MM patient bone marrow
- Show efficacy against antibody-resistant multiple myeloma cells in ex vivo patient samples
- First-line, MRD(+), post– transplant patients
- Goal to convert MRD(+) patients to MRD (-) at day 100 post-transplant
- Conversion to MRD (-) is the best correlation for curative therapy
We have initiated research collaborations with US-based Celularity Inc. and South Korea-based GC LabCell to investigate allogeneic NK cell combinations in multiple indications.