Northwestern University Robert R. McCormick School of Engineering and Applied Science

Evan A. Scott Research Group

Development of immunoengineering tools for controlled immunomodulation

LaserCell*One component of our toolbox: Optofluidic rupture of polymersomes for precise spatiotemporal endosomal or cytosolic delivery of antigen and adjuvant. For more details see Vasdekis & Scott et al. ACS Nano. 2012

Few therapeutic strategies can rival vaccination in terms of effectiveness at treating and preventing infectious diseases. Often only a few doses is required to achieve life-long resistance to certain infections.  Unfortunately, despite a strong track record of success over the past century for the eradication of numerous lethal and high morbidity human diseases, we still do not have a clear understanding of how the process of vaccination works.  As a result, modern vaccines are still developed using costly and time consuming trial and error approaches, and despite years of effort we are currently unable to vaccinate against many of our most serious threats including HIV, malaria, and hemorrhagic fever arenaviruses such as Ebola and Lassa.  Additionally, common bacterial infections are becoming steadily more difficult to treat due to acquired resistances to antibiotics.  In theory, strategies used to generate vaccines against pathogens should also be applicable to cancer therapies, but immunotherapies to cancer have demonstrated limited and at best inconsistent results.  We urgently need a better understanding of the mechanisms behind vaccination in order to more rapidly and successfully develop vaccines using principles of rational design.

 Vaccination is essentially a means of training our immune system to find and destroy infectious agents, and thus our understanding of vaccination is intimately linked to our understanding of immunobiology.  The immune system has evolved to detect, analyze, and destroy diverse pathogens and dysfunctional cells, such as cancer cells, while remaining tolerant to healthy self-tissues. Only for the past few decades have we known that the center of this process that determines the necessity, type and intensity of an immune response is the professional antigen-presenting cell (APC), which includes dendritic cells (DCs), macrophages, and B-cells.  These cells function as sentinels that engulf and analyze different molecules and particulates in our bodies.  Depending on various signals that these cells receive either from circulating hormones, proteins present in the matrices of our tissues, other cells, or from foreign fragments of bacteria, fungi, or viruses, APCs can induce immunogenic or tolerizing responses.  Thus comprehension of how these cells process biochemical cues from their environment and subsequent manipulation of these cues can allow modulation of immune responses for improved therapies and treatments of disease.  Such research would have broad and far-reaching applications in the areas of cancer, vaccination and autoimmunity as well as enhance our understanding of how our immune system functions.

As immunoengineers, we propose the use of techniques and principles from bioengineering, chemistry, and biology as a multidisciplinary approach to the study of vaccination, with a goal of furthering basic understandings of immunobiology and developing clinically translational approaches to immunotherapy.  Our work will focus on examining how these APCs receive and process signals from their environment and develop techniques to control and initiate such signals in order to induce controlled immune responses. We intended to generate an immunotherapeutic toolbox that can be used to tailor therapies for specific diseases and demonstrate their efficacy against models for cancer.