B7-DC Variants in the Stimulation of Immune Responses

Unmet Need
Unfortunately, many human tumor cells have evolved ways of deactivating the body’s immune system by expressing inhibitory signals (e.g., PD-L1, CTLA-4) on tumor cell surfaces. As a consequence, there is a pressing need for novel immunotherapies that would allow immune cells to bypass specific inhibitory signals on tumor cells and carry out their primary protective functions. Development of a new method and approach to amplify innate immune responses against cancer and infections would have broad applications in treating human diseases.

Technology Overview
B7-DC (PD-L2) belongs to the B7 costimulatory molecular family found on immune cell surfaces (and some solid tumor types) and has a high binding affinity for the programmed cell death protein 1 (PD-1) receptor. Tumor cells expressing PD-L2 can engage and deactivate adaptive immune cells through PD-1 to evade detection and destruction.

Johns Hopkins researchers generated human B7-DC polypeptide variants with altered amino acid sequences which reduced the binding to PD-1, but retained its ability to co-stimulate T cells (i.e., increasing antigen-specific proliferation of T cells, enhancing cytokine production by T cells, stimulating differentiation and effector functions of T cells and/or promoting T cell survival). Such B7-DC variants may allow immune T cells to eliminate tumor cells and effectively stimulate immune responses including those against viral and bacterial infections.

Stage of Development
In vitro and in vivo data is available.

Publications
Wang S et al. J Exp Med. 2003 May 5;197(9):1083-91.
 

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