Two Johns Hopkins research teams have received technology development grants totaling approximately $200,000 through the Louis B. Thalheimer Fund for Translational Research.

Finalists pitched their proposals virtually in late May to an outside panel of independent researchers and investors, innovation executives and venture investors. Established through a generous $5.4 million gift from businessman and philanthropist Louis B. Thalheimer, the fund provides seed funding for vital proof-of-concept and validation studies of Johns Hopkins technologies.

Since 2016, the Thalheimer Fund has awarded more than $1.7 million to 20 projects at Johns Hopkins. Grants range from $25,000 to $100,000, and all recipients have formally reported their inventions to JHTV. Previous Thalheimer winners are developing a faster and more accurate way to diagnose epilepsy; an oral therapy for patients suffering from inflammatory bowel disease; and a longer-lasting treatment for wrinkles and migraines, among other technologies.

This year’s grantees are:

Principal Investigator:
Jonathan P. Schneck, M.D., Ph.D.
Institute for Cell Engineering, Sidney Kimmel Comprehensive Cancer Center, Center for Translational ImmunoEngineering, and Department of Pathology, School of Medicine

Co-Principal Investigator:
Hai-Quan Mao, Ph.D.
Institute for NanoBioTechnology and Department of Materials Science and Engineering, Whiting School of Engineering; Department of Biomedical Engineering, School of Medicine

The pitch:
Lipid Nanoparticles Targeting Tumor-Specific CD4+ T-Cells for In Situ CAR T-Cell Generation for Immunotherapy

Jonathan Schneck’s research focuses on the basic mechanisms that control immune responses. Specifically, he studies how cytotoxic T-cells, known as killer T-cells — cells that help eliminate infections or cancers — get activated, recognize their targets and get turned off again. His team focuses on how to manipulate the immune system with the hopes of designing improved anti-cancer therapies by ramping up the immune system or treating autoimmune disease and transplant patients with better immune system suppression.

Chimeric antigen receptor (CAR) T-cells developed in labs have demonstrated remarkable clinical efficacy in the blood-born cancers leukemia, lymphoma and multiple myeloma, with long-term remission and even cure being observed.

There are currently six Food and Drug Administration-approved CAR therapies, all utilizing T-cells to target B-cell lymphoma or multiple myeloma. Despite the remarkable impact of these engineered cell products, they are still hindered by barriers that limit their use as mainstream cancer therapies, specifically the lengthy and costly ex vivo cell production, tumor antigen escape, and having little to no efficacy in solid tumors.

Furthermore, manipulating antigen-specific-T cells in vivo is a significant challenge due to the lack of appropriate targeting and efficient delivery platforms.

Schneck and Hai-Quan Mao, along with Ph.D. candidates Joseph Choy and Yining Zhu, have proposed to use a novel nanoparticle platform for highly specific mRNA delivery to T-cells — jointly developed in their laboratories to overcome these barriers — and to create an efficacious therapy for solid tumors. The platform will selectively expand tumor specific CD4+ T-cells while simultaneously endowing them with a CAR in vivo, enabling dual recognition of cancer cell antigens while minimizing deleterious side effects. As a nonviral T-cell transfection approach, the platform itself represents a major advance and can herald new ways of genetically manipulating T-cells in addition to endowing them with CAR T-cell qualities.

While the proposed study will focus on CD4+ T-cells, this platform is versatile and can be tailored to target, transfect, and expand antigen specific CD8+ T-cells as well.

If successful, this disruptive technology has the potential to revolutionize cancer immunotherapies as an off-the-shelf therapeutic modality and overcome the cost, safety and efficacy barriers of existing CAR T-cell therapies.

Principal Investigator:
Shoji Hall, Ph.D.
Department of Materials Science and Engineering, Whiting School of Engineering.   

 The Pitch:
High-Performance Electrochemical Reduction of CO2 to CO By Electrodeposited CuZn4

The Hall group is committed to enhancing the field of electrocatalysis by studying electrified solid-solution interfaces. The team uses ordered intermetallic materials, known for their distinct compositions and long-range atomic-scale ordering, to gain insight into electrocatalyst structure and function. Intermetallics stand as an unparalleled platform for an in-depth examination of material structure and functionality, differentiating them from more typical material systems, which are poorly defined. Synthesizing intermetallic nanomaterials is challenging. To address this, the Hall Group is developing methods to produce nanostructured, ordered,= intermetallic compounds under ambient conditions. Concurrently, it is engaged in understanding the role of water in modulating proton transport and how the interfacial water structure influences electrochemical reactivity.

Hall’s team has achieved a significant breakthrough in sustainable chemistry with the development of ordered intermetallic CuZn4 (a copper/zinc compound), a highly efficient and cost-effective catalyst that enables the electrochemical reduction of carbon dioxide (CO2) into valuable carbon monoxide (CO) using renewable electricity as the energy source.

This innovative process takes place at room temperature and atmospheric pressure, simplifies the production, and eliminates the need for expensive temperature and precious metal catalysts such as silver (Ag). To catalyze the chemical reaction, CO2 is passed through a gas diffusion electrode made of a porous carbon paper, allowing the gas to interact with the CuZn4-electrolyte interface. When a voltage below the reduction potential of CO2 is applied to the catalyst, the CO2 is converted to CO gas through reduction.

This breakthrough has profound implications for the future of sustainable manufacturing and offers a promising path towards a more sustainable and carbon-neutral future. The unique advantages of the process are:

CuZn4 catalysts can be tailored to have high selectivity for the electrochemical reduction of CO2 to CO. The unoptimized system can achieve similar metrics for CO selectivity, compared to Ag-based systems that are currently being tested in pilot plants. The system offers the potential for greater cost-effectiveness (because of its lower price for raw materials) and high-energy efficiency, with comparable or even better selectivity to CO.

The CuZn4 catalyst is manufactured using electrodeposition, which allows for electrode areas ranging from a few square centimeters to several square meters to be accessed. The scalability of our process is due to the ease of producing the electrodeposited catalysts. This makes the CuZn4 catalyst an attractive option for industrial-scale CO2 reduction to CO, as it can be easily scaled up to match the needs of the industrial processes.