Amgen’s acute lymphoblastic leukemia treatment, Blincyto, coasted past the FDA bottleneck ahead of schedule, gaining approval earlier this month as a “first of its kind” immunotherapy. The FDA designated Blincyto as a breakthrough therapy and an orphan product on top of granting a priority review, thus propelling the bispecific antibody (BsAb) to the market five months early.

The swift approval and technology behind this monoclonal antibody (mAb) hybrid caught our eye here at WEEKLY, so let’s break down the science behind Blincyto.


A bispecific antibody is a genetically engineered protein composed of two different monoclonal antibody fragments.

The descriptor bispecific derives from  mAb’s unique ability to bind two different types of antigens. Traditional monospecific mAbs have affinity for only one target. A bispecific antibody has specificity for a target cell on one arm and a therapeutic (or killing agent) on the other.


Cytotoxic T-cells (more commonly referred to as killer T-cells) can be thought of as the warriors of the immune system. They compose the front-line of the specific immune response, activated to attack foreign invaders. Normally, this activation occurs when a unique T-cell receptor recognizes a specific target protein.

Once activated, cytotoxic T-cells can become highly effective cancer killing machines. There is a catch: T-cells often miss tumor cells because they are not considered by the body to be foreign. The drug discovery challenge lies in figuring out how to create an army of tumor-specific T-cells.


Blincyto redirects killer T-cells to target specific tumor cells. How? One arm grabs CD19, a protein found on the surface of blood cancer cells, and the other arm targets CD3, a protein that activates the T-cell receptor complex.

The above image represents the two arms of a BsAb.

Bringing the CD19 and CD3 together ensures killer T-cells are triggered to target the cancer cells. Activation also induces T-cell proliferation and the descendants of the activated T-cell also target the tumor cells.


The European Medicines Agency is ahead of the curve with two BsAb approvals under their belt. Neovii Biotech’s (Grafelfing, Germany) Removab fights malignant ascites—a fluid buildup as the result of a tumor. Active Biotech’s (Lund, Sweden) Anyara knocks out cancerous cells in renal cell carcinoma.

With the stateside debut of BsAbs underway, plenty of other companies are looking to jump into the mix: TRION Pharma (Munich, Germany), Amgen (Thousand Oaks, CA), AbbVie (North Chicago, Illinios), Ablynx (Ghent, Belgium), Affimed (Heidelberg, Germany), and MacroGenics (Rockville, MD) all have BsAbs in development. While the majority of the BsAb pipeline targets cancer, about 25% go after rheumatoid arthritis, other autoimmune disorders, and respiratory disease.

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