Human mast cells as a platform for new cancer immunotherapy strategies

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ABSTRACT The role of human tissue mast cells (MC) in the pathology of many cancers is not known. Correlative studies in humans have found high MC numbers in the tumor microenvironment have pro- and anti-tumor effects and contrasting patient outcomes depending on the cancer types. We discovered that human MC, are activated by, and promote killing of, cancer cells in vitro and in vivo, infiltrate solid cell tumor masses, bind to tumors in vivo, can be obtained in quantities necessary for patient infusion, cryopreserved without loss of function, and display no overt toxic effects when injected intravenously into mice with engrafted human tumors. To develop this novel, cell-based cancer immunotherapy we will utilize FDA approved humanized IgE (which bind MC FcεRI with extremely high affinity) to target MC to cancer cells. This new approach is premised on efficient, autologous production of MC, tumor targeting, and effective tumor specific killing. This strategy has not been feasible heretofore as these cells reside in tissue and cannot be obtained for autologous use. Our overall hypothesis is tumor targeted MC will bind to cancer cells in vitro and in vivo after intratumoral or intravenous administration and elicit significant anti-tumor activity. Here we will determine the in vitro and in vivo activity of human MC against several cancer types. These studies could lead to new adoptive cell therapies for diverse cancers ranging from lymphoma to breast cancer.