Bispecific Antibodies

Antibodies are found naturally in the blood stream to fight infections. Monoclonal antibodies (mABs) are similar to normal antibodies but are created in the laboratory. Monoclonal antibodies are directed against specific proteins that are exclusively, or excessively present on the cell surface of cancer cells. A bispecific antibody is a particular form of mAB that is able to bind two different antigens (the part of the target an antibody attaches to) at the same time.

The first bispecific antibody that was introduced in the treatment for patients with hematological malignancies consists of blinatumomab (Blincyto®). This agent is used in the treatment of patients with acute lymphocytic leukemia (ALL) and has a binding site for CD3, a protein on the surface of T-lymphocytes, and CD20, a protein that is found on the surface of cancerous B-cells. By combining these two targets, blinatumomab is able to couple a malignant B-cell to an activated T-cell, leading to the destruction of the cancerous cell.

Teclistamab (Tecvayli®) has recently entered the treatment landscape for patients with multiple myeloma in whom previous treatments failed. Teclistamab is a bispecific antigen that has a binding site for CD3, expressed on the surface of T-lymphocytes, and BCMA, a protein that is exclusively found on the cell surface of myeloma cells. As such, this agent helps T-lymphocytes to recognize multiple myeloma cells and destroy them.

Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 which has recently been approved for the treatment of previously treated patients with follicular lymphoma. The mode of action of this agent is similar to what was described for blinatumomab and teclistamab.

In addition to these agents, many more bispecific antibodies are in the pipeline

Bispecific antibodies are associated with a specific set of potential side effects. One of the more prominent of these adverse events consists of the cytokine release syndrome (CRS), which is the result of an an overactivation of the immune system. CRS occurs rapidly after the start of therapy and can lead to fever, nausea, headaches, a low blood pressure and breathlessness. In addition to this, bispecific antibodies are associated with a low risk for neurological side effects (ICANS: immune effector cell-associated neurotoxicity syndrome). This can manifest itself as speech difficulties, a tremor, confusion, or even coma. Other common side effects with these agents include infections and reduced blood counts.