The Hartwell Foundation

 

2020 Biomedical Research Collaboration Award

Memphis, TN, January 6, 2020 -- The Hartwell Foundation officially announced the winners of a Biomedical Research Collaboration Award to Justin J. Taylor, Ph.D., 2015 Hartwell Investigator Assistant Member, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA and Minglin Ma, Ph.D., 2015 Hartwell Investigator and Associate Professor, Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY for their proposal "Preventing Lethal Infections in Children Recovering from Cancer Therapy". The researchers will receive $787,153 in combined direct cost over three years.

Each year, around 2,000 U. S. children receive stem cell transplants to replace their immune system following irradiation to treat cancer. Unfortunately, stem cells take 6-12 months to fully replace the immune system, leaving the children incredibly vulnerable to infection, particularly viral infections. The immunocompromised individuals cannot be vaccinated effectively and the few available treatments for viral infection often suppress the clinical replacement of the immune system, increasing further risk of other severe bacterial and fungal infections. In fact, more than half of all children receiving transplants are hospitalized for serious infections due to their immunocompromised state, which each year leads to more than 300 affected children dying from viral infections.

To address the unmet need for preventing lethal viral infections in children recovering from cancer therapy, Justin and Minglin propose to genetically engineer the body's own infection-fighting white blood cells (B lymphocytes) to produce potent and long-acting antibodies against specific viruses. They propose to use a removable biocompatible encapsulation device of their design to retain the engineered B cells and support cell survival following transplantation into a host recipient. Encapsulation of the B cells will protect the cells from destruction by the recipient immune response and allow the protective antibodies produced by the bioengineered B cells to escape into the blood circulation to provide immediate and long-lasting immunity.

In theory, the Taylor-Ma technologies will allow B cells from any person to be transplanted to an immunocompromised host without the need to match the donor, thus enabling access of the technology to a wide audience of potential recipients. If Justin and Minglin are successful, it will be possible to reduce the risk of severe viral infections in immunocompromised children recovering from cancer therapy; infections that contribute to unnecessary hospitalization, reduction in quality of life and childhood mortality.

Justin Taylor is an immunologist whose research focuses on B cells, a type of white blood cell responsible for producing immune proteins called antibodies. He seeks to understand how B cells produce protection in response to vaccination and infection and whether by using cell engineering they can be mobilized to do so in specific ways.

Minglin Ma is a bioengineer that specializes in rational design, synthesis, characterization and fabrication of materials for innovative therapeutic and diagnostic applications. His research explores issues at the frontier of health and sustainability, including cancer and diabetes.

As a 2015 Hartwell Investigator, Justin Taylor proposed a paradigm-shifting biotechnology strategy to engineer B cells to provide life-long protection against viral infection without reliance on a vaccine. Using cutting-edge genetic engineering (CRISPR/Cas9 mediated replacement), he reprogramed B cells to cease production of native DNA-encoded antibodies by inserting DNA that encoded an ideal anti-virus monoclonal antibody. His approach was a significant departure from classic vaccine design because it didn't rely on the chance production of a neutralizing antibody in the patient, but instead relied on the patient's own B-cells to achieve immediate and life-long protection against an otherwise resistant pathogen. Focusing first on respiratory syncytial virus (RSV), a leading cause of severe respiratory illness in young children and for which all attempts to develop an effective vaccine have so far failed, Justin was able to successfully and efficiently demonstrate the expression of protective antibodies against RSV.

As a 2015 Hartwell Investigator, Minglin Ma proposed a retrievable and scalable encapsulation device to enable the transplantation of insulin-producing pancreatic islet cells for the treatment of juvenile diabetes. His device was designed to protect the islets from destruction by the host immune system and at the same time enable an active insulin response to elevated blood glucose. Called cellular thread, his design was based upon the way certain spiders create a silk fiber to collect drinking water. Minglin was able to demonstrate how the fabricated device with encapsulated islets had robust mechanical properties, promising biocompatibility and sustainable functional performance in a diabetic mouse model; and that human islets encapsulated in the device retained high cell viability in immunodeficient rodent models. He seeks now to evaluate the technologies in a clinical trial.

The Hartwell Foundation seeks to inspire innovation and achievement by offering individual researchers an opportunity to realize their professional goals. Fostering unique collaborations, between investigators of complementary scientific strengths at different Hartwell participating institution, is one objective of The Hartwell Foundation in its mission to fund innovative, early-stage applied biomedical research with the potential to benefit children of the United States.

For additional information see www.thehartwellfoundation.org

Biomedical Research Collaboration Awards

Individual Awards