Investigating the effects of targeted chimeric antigen receptor natural killer cells armored with tumor-attracting chemokine receptors combined with a novel immunomodulator in the treatment of osteosarcoma
Mentor Name: Mitchell Cairo
Children and adolescents with poor risk osteosarcoma (Relapsed/Refractory or R/R) remain a challenge to cure with conventional treatments due to their dismal outcomes. In this project, we will work on developing immunotherapies for poor risk R/R osteosarcoma based on exploiting innate immunity. We will use a novel target named melanoma cell adhesion molecule (MCAM), which is commonly expressed by osteosarcoma tumors, and Chimeric Antigen Receptor (CAR) natural killer (NK) cells as the primary final driver of tumor regression. We hypothesize that we can enhance CAR NK-mediated killing of pediatric solid tumors through the use of strategic combinatorial immunotherapy to overcome tumor microenvironment resistance. The hypothesized combinatorial immunotherapy will consist of CXCR2 and tri-specific killer engagers (TriKEs). We will armor CAR NK cells with a tumor-attracting chemokine receptor, CXCR2 (ligand to IL-8), to improve tumor infiltration of CAR NK cells. Additionally, we will incorporate the use of TriKE, an immunomodulator.
