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Immunotherapies for Life

Bispecific Antibodies

Bispecific antibodies (BsAb) can fulfill an unmet need. A single chain Fv fragment (scFv) is constructed from the VH and VL portions of an antibody. When an IgG anti-tumor antibody is linked to the scFv of anti-CD3, a BsAb is formed. CD3 is an activation receptor on all T-cells. Besides cross-linking tumors to T-cells, a BsAb signals T cells to adopt its killer mode. 

CD3 engagement also induces T-cell proliferation and generation of effector cytokines that potentiate the anti-tumor effect. Picogram quantities of BsAb have been proven to exert significant anti-tumor effects in vitro and in vivo in preclinical animal models and in patients.

A critical component of an effective BsAb is the tumor-specific antibody, which has to bind to a surface antigen. The antigen should not be released or be freely circulating in the blood in order to avoid impeding antibody-tumor binding.

The tumor antigen ideally should be independent of HLA, present on cancer stem cells if cancer is to be eradicated at its source. Other important properties of the anti-tumor antibody include high affinity, low cross-reactivity and robust stability. Both the antigen GD2 and B7-H3, and their humanized antibodies hu3F8 and hu8H9 fulfill all of these criteria and are therefore ideal for building BsAb.

Our bispecific platform technology has substantial benefits over the existing technologies in terms of tumor targeting, immune activation, and serum half-life.