Description:

The Departments of Pharmacology and Biomedical Engineering are pleased to welcome our faculty candidate, Dr. Michael Mitchell.

Michael Mitchell, PhD
Postdoctoral Fellow
Department of Chemical Engineering
Koch Institute for Integrative Cancer Research
Massachusetts Institute of Technology

The following, is an overview of this seminar, as described by Dr. Mitchell:

It has become apparent that the surrounding tumor microenvironment can promote the growth, drug resistance, and metastasis of malignant cells. In this talk, I will discuss how cells within the vascular and bone marrow microenvironments can be engineered and exploited for cancer therapy. I will first discuss an approach to engineer the surface of innate immune cells in the bloodstream with cancer therapeutics in vivo. Mimicking the cytotoxic activity of natural killer cells, the approach exploits the extensive surface area of circulating immune cells to display both the cancer-specific TNF-related apoptosis-inducing ligand (TRAIL) and E-selectin adhesion receptor to metastatic cells in the vascular microenvironment. The resulting “unnatural killer cells” neutralized tumor cells within the circulation in vivo, and prevented metastatic tumor formation in spontaneous metastasis mouse models of prostate cancer. I will then present our most recent work on the development of gene delivery materials that target the bone marrow microenvironment in vivo, as a means to treat cancers that colonize in marrow. Through the synthesis of a diverse library of polymer-lipid hybrids in combination with high throughput in vivo screening methods, we have identified novel biomaterials that efficiently deliver nucleic acid therapeutics to target cells in the bone marrow microenvironment at low dosages. By targeting physical interactions between tumor cells and the surrounding microenvironment, these materials disrupted multiple myeloma progression in clinically relevant, humanized mouse models of the disease.