HVEM Muteins for Cancer and Other Uses

Development and testing of HVEM muteins could be the key to advancing cancer immunotherapy treatments

B lymphomas are cancers that affect the body’s B cells, the lymphocytes that produce antibodies. There are many kinds of B cell lymphomas, and they can strike people of any age. There is an urgent need for cancer immunotherapies to help these patients.

HVEM is a type of tumor necrosis factor (TNF) receptor expressed by B cells and other cell types. This receptor can both transmit and receive signals. HVEM is highly mutated in B lymphomas, where it may act as a ligand for one of its binding partners, a molecule called a B and T lymphocyte attenuator (BTLA). Researchers have found that HVEM-BTLA in fact drives B cell responses and growth and is one pathway responsible for B lymphomas. Therefore, restoring HVEM interactions could be important.

At La Jolla Institute for Immunology, Professor Mitchell Kronenberg, Ph.D., is investigating how to develop forms of HVEM that could engage BTLA without engaging its other ligands, to prevent off target effects.

The Kronenberg Lab has succeeded in developing HVEM muteins that work in vitro in mice. The researchers have tested them in vivo to examine inflammation and anti-bacterial responses.

The lab is continuing to develop protein engineering techniques to further establish and test the HVEM mutein. A composition of matter patent has been filed for the invention. With further support, the group aims to prepare and test human versions of the muteins.