Bispecific Antibodies in Cancer

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Interest in these bioengineered antibodies has been rekindled by the striking success seen in the treatment of some cancers with immunotherapies.
Interest in these bioengineered antibodies has been rekindled by the striking success seen in the treatment of some cancers with immunotherapies.

Bispecific antibodies, as the name suggests, simultaneously target 2 or more tumor antigens on the same or separate cells to disrupt cancer development or progression. Others engage and tether cancer cells and immune cells together to increase cancer-cell destruction.

No matter the strategy researchers take, however, interest in these bioengineered antibodies has been rekindled by the striking success seen in the treatment of some cancers with immunotherapy — notably, checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapy — in the past few years.

“Bispecific antibodies were stalled for a bit, but in this new era of immunotherapy, there's definitely renewed interest,” said Nikhil Munshi, MD, a medical oncologist at Dana Farber Cancer Institute and director of basic and correlative science at the Jerome Lipper Multiple Myeloma Center in Boston, Massachusetts. “And, we have newer, more modern methodologies that have propelled the field forward.”

An estimated 50 clinical trials using bispecific antibodies for various malignancies are now underway, while biotechnology companies and academic labs purportedly have hundreds of different products in development and awaiting testing.1

Still, the US Food and Drug Administration (FDA) has approved only 1 bispecific antibody with a cancer indication so far, underscoring the need for further research, before these targeted biologics can emerge as viable and less costly alternatives to other types of immunotherapy that are highly tailored to an individual's cancer.

In July 2017, the FDA approved Amgen's bispecific antibody, blinatumomab (Blincyto) for acute lymphoblastic leukemia (ALL) in adults and children with advanced disease.2 Blinatumomab targets and binds 2 proteins, one, CD19, that is found on the surface of B-lineage cells and the other, CD3, that is found on T cells — essentially bringing the 2 in close enough proximity that T cells better recognize leukemic cells to kill them.

Other investigators are using similar tacks in creating these dual-targeting agents.

Researchers at The Ohio State University Comprehensive Cancer Center in Columbus, for example, used an approach comparable to blinatumomab in a humanized mouse model for multiple myeloma, according to Ilan Zipkin, PhD, a vice president at the Parker Institute for Cancer Immunotherapy in San Francisco, California. But the investigators extended the approved drug's approach, he says, by tethering a common tumor antigen in this cancer, CS1, to a receptor, NKG2D, expressed on several types of immune system cells that kill.

Dr Zipkin wrote in an email that the Ohio researchers “are showing activity with a bispecific that promotes several different cell types to kill the myeloma cells,” including, importantly, natural killer cells. Results of that study were among those highlighted at the American Association for Cancer Research Annual Meeting in Chicago, Illinois, earlier this year.3

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