Bispecific antibodies in cancer immunotherapy

Abstract

Cancer immunotherapy has recently generated much excitement after the continuing success of the immunomodulating anti-CTLA-4 and anti-PD-1 antibodies against various types of cancers. Aside from these immunomodulating antibodies, bispecific antibodies, chimeric antigen receptor T cells, and other technologies are being actively studied. Among the various approaches to cancer immunotherapy, 2 bispecific antibodies are currently approved for patient care. Many more bispecific antibodies are now in various phases of clinical development and will become the next generation of antibody-based therapies. Further understanding of immunology and advances in protein engineering will help to generate a greater variety of bispecific antibodies to fight cancer. Here, we focus on bispecific antibodies that recruit immune cells to engage and kill tumor cells.

Keywords: NK cells; T cells; bispecific antibody; cancer; heterodimerization; immunotherapy; scFv; single domain antibody.

Figure 1.

Mechanisms of action of bispecific antibodies. BiTE and TrioMab are shown here to demonstrate the tumor cell killing induced by bispecific antibodies. T cells or NK cells are recruited to the proximity of tumor cells by bispecific antibodies. Engaged T or NK cells will then attack tumor cells and lead to cytotoxicity, while non-engaged T cells or NK cells remain inactive toward the tumor cells.

Figure 2.

Diverse formats of bispecific antibodies. Heavy chains are shown in dark shades of black, gray, orange or green, while corresponding light chains are in lighter shades of the same colors. Peptide linkers are shown in thin black lines and engineered disulfide bonds by thin green lines. Heavy chain mutations are shown with dark gray triangles. Approximate molecular weights are estimated assuming ∼12.5 kDa per immunoglobulin domains.