Expansion and availability of an increased number of functionally competent anti-myeloma immune effectors capable of myeloma killing represent a desirable concept for therapeutic efficacy of HSCT. In addition to T cells, natural killer (NK) cells have been appreciated as contributors in the eradication of myeloma after HSCT. This project will explore NK cell alloreactivity and direct stimulation of effector functions by agonist mAb as two promising strategies to promote myeloma killing and improve outcome of HSCT. NK cell alloreactivity is based on mismatching of killer-cell immunoglobulin-like receptor (KIR) ligand with their donors which has potential to kill recipient-derived cancer. Direct stimulation of effector function by agonist antibody against CD137 shows promising efficacy and safety in cancer patients. Our recent data also suggest that agonist stimulation by CD137 antibody delivery strong anti-myeloma effects in myeloma-bearing mice. Because HSCT remains only potentially curative treatment for MM patients, HSCT is attractive combinatorial partner with agonist CD137 therapy. This project will elucidate the ability of NK cell alloreactivity and direct stimulation of effector functions by agonist CD137 antibody to specifically and effectively eliminate myeloma after HSCT.
- This project is suitable for PhD student.