Therapeutic Immunotoxins for the Treatment of T Cell Malignancies

Abnormal T lymphocyte (T cell) function, including tumor formation in T cells, can lead to a wide variety of diseases. Over 100 million people worldwide suffer from T cell autoimmune disorders of varying severity, such as lupus and graft-versus-host disease, and the incidence of T cell-mediated cancers, including lymphomas and leukemias, has risen over the past decade. These diseases can be deadly, and not all patients respond to standard therapies. New treatment options and more advanced therapies are needed for patients with T cell-mediated diseases to increase their chances of survival and improve their quality of life. 

The transferred technology describes T-cell targeting immunotoxins developed in the laboratory of Dr. David Neville, Jr. at the National Institute of Mental Health (NIMH). The immunotoxin proteins consist of two portions: a targeting antibody that directs the immunotoxin to T cells and an exotoxin aimed at destroying the targeted T cells. These immunotoxins could be potentially useful in treating any disease or abnormality caused by T cells. The transferred technology also involves a high-yield, low-cost immunotoxin expression system whereby functional immunotoxins can be produced in mutant yeast strains. 

The development of these immunotoxin technologies was realized through an extensive collaborative research effort. During the early stages of the technology, Dr. Neville and NIMH established collaborations with two prestigious academic institutions and a major commercial partner through a four-way Cooperative Research and Development Agreement (CRADA). Later, another well-known nonprofit institution made the CRADA a five-way collaboration to help with late preclinical and clinical studies. Very early in the clinical testing, the commercial partner terminated the CRADA and the license. Without the commercial contributions, it appeared that development of this promising therapy would stall before its medical potential could be realized. 

In March 2010, NIH transferred rights to the immunotoxin intellectual property to Angimmune, LLC, through an exclusive license. After retiring from 48 years of federal service, Dr. Neville co-founded Angimmune to further develop the immunotoxins he invented during his federal career. Under the direction of Dr. Neville, Angimmune initiated new clinical studies with the lead immunotoxins and showed their effectiveness in clinical trial patients. Without Dr. Neville’s passion to realize the therapeutic potential of this technology through his inventive federal research and in his licensing efforts at Angimmune, clinical research of this technology would have ceased, ending the hope of a future marketed drug. 

Awardees

National Institute of Mental Health

• Dr. David Neville, Jr.

NIH Office of Technology Transfer

• Dr. Samuel Bish