The processes of tumor invasion and establishment of distant metastases are the boundaries beyond which manageable cancers become untreatable; tumor associated macrophages (TAMs) are critical to enable and sustain these growths. TAMs have been correlated with tumor angiogenesis, invasion and metastasis, and poor patient prognoses. They have also been shown to home to and silence the immune response to tumors. In our work, we are taking advantage of their innate characteristics and manipulating macrophages for: (1) their use as imaging and delivery agents (2) therapeutic entities in and of themselves. Toward the first aim, we present effects of surface functionalization of macrophages via various chemical methods, demonstrating that the cells retain viability, along with their homing and phagocytic characteristics. These cells also continue to migrate to and interact with cancer models, in vitro and in vivo. In the second objective, we have converted macrophages into enhanced tumor-fighting entities by employing an arginine-nanoparticle CRISPR-Cas9 delivery system in order to knock out SIRP-a, or the “don’t eat me” signal. The edited cells possessed enhanced abilities to phagocytose cancer cells. This cell based platform will lay the ground-work for the generation of new cell based entities that can be used to image and treat cancers, with enhanced specificity and tumor penetration.

Modified macrophages as cell-based delivery tools and therapeutic entities for cancer study and treatment

2019 Spring National Meeting

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