Jeffrey Hubbell

2023-06-27 Assigned to THE UNIVERSITY OF CHICAGO reassignment THE UNIVERSITY OF CHICAGO ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HUBBELL, JEFFREY, ISHIHARA, Ako, ISHIHARA, JUN, WATKINS, Elyse, YUBA, Eiji

Immunoengineering is a rapidly evolving field that has been driving innovations in manipulating immune system for new treatment tools and methods. The need for materials for immunoengineering applications has gained significant attention in recent years due to the growing demand for effective therapies that can target and regulate the immune system. Biologics and biomaterials are emerging as promising tools for controlling immune responses, and a wide variety of materials, including proteins, polymers, nanoparticles, and hydrogels, are being developed for this purpose. In this review article, we explore the different types of materials used in immunoengineering applications, their properties and design principles, and highlight the latest therapeutic materials advancements. Recent works in adjuvants, vaccines, immune tolerance, immunotherapy, and tissue models for immunoengineering studies are discussed.

The only FDA-approved oral immunotherapy for a food allergy provides protection against accidental exposure to peanuts. However, this therapy often causes discomfort or side effects and requires long-term commitment. Better preventive and therapeutic solutions are urgently needed. We develop a tolerance-inducing vaccine technology that utilizes glycosylation-modified antigens to induce antigen-specific non-responsiveness. The glycosylation-modified antigens are administered intravenously (i.v.) or subcutaneously (s.c.) and traffic to the liver or lymph nodes, respectively, leading to preferential internalization by antigen-presenting cells, educating the immune system to respond in an innocuous way. In a mouse model of cow's milk allergy, treatment with glycosylation-modified β-lactoglobulin (BLG) is effective in preventing the onset of allergy. In addition, s.c. administration of glycosylation-modified BLG shows …

The disclosure is directed to methods of inhibiting coronavirus infection using a hydrocarbon stapled peptide which is a peptidomimetic of the human angiotensin-converting enzyme 2 (hACE2). The hydrocarbon stapled peptide binds to the receptor binding domain (RBD) of a coronavirus spike protein (S) and inhibits binding of the coronavirus to hACE2 expressed on the surface of host cells.

Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients that reduces efficacy and increases adverse reactions. Our laboratory has shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer, p(Man). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We find that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by T regulatory cells. We identify increased T cell receptor signaling and increased apoptosis and …

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The interface between immunology and engineering, that is, immunoengineering, is becoming fertile ground for innovation. Engineering comes into play when basic science has progressed such that design rules can be discerned. One can find examples of immunoengineering in the design of molecular therapeutics, delivery systems for molecular and cellular therapeutics, cellular therapeutics themselves, and experimental and computational analytical systems to tease out new aspects of basic immunology, leading to new design rules. In the realm of immunoengineering there are notable applications for both prophylactic and therapeutic purposes. These include the development of molecular and nanomaterial vaccines for infectious disease prevention and cancer treatment. These materials also play a role in creating inverse vaccines to address conditions such as autoimmunity and allergies, or counteracting …

Therapeutic vaccination has long been a promising avenue for cancer immunotherapy but is often limited by tumor heterogeneity. The genetic and molecular diversity between patients often results in variation in the antigens present on cancer cell surfaces. As a result, recent research has focused on personalized cancer vaccines. While promising, this strategy suffers from time-consuming production, high cost, inaccessibility, and targeting of a limited number of tumor antigens. Instead, we explore an antigen-agnostic polymeric in situ cancer vaccination platform for treating blood malignancies, in our model here with acute myeloid leukemia (AML). Rather than immunizing against specific antigens or targeting adjuvant to specific cell surface markers, this platform leverages a characteristic metabolic and enzymatic dysregulation in cancer cells that produces an excess of free cysteine thiols on their surfaces …