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Honoring the Scientist Who Pioneered the BiTE® Antibody Construct

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  • 08/03/2015
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  • Source: Amgen

Honoring the Scientist Who Pioneered the BiTE® Antibody Construct

It’s rare for a scientist to discover a molecule that leads to a new medicine, and rarer still to discover a whole new type of drug modality. In the case of Amgen and the work that led to the BiTE® antibody construct, that person is Peter Kufer. 

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From left, Sasha Kamb, Peter Kufer, and David Lacey after presenting Kufer with the David L. Lacey Award for his work on the BiTE® antibody construct.

Kufer, who is now executive director and site head at Amgen Research Munich (ARM), was the first person who figured out how to create a BiTE® antibody construct, way back in 1994 while working at the University of Munich. BiTE® antibody constructs—bispecific T cell engagers—are a type of fusion protein that is designed to harness the power of the body’s immune system to treat cancer. This new treatment modality has shown encouraging potential against a range of cancers.

These bispecific constructs are created by linking the targeting regions of two antibodies. One arm of the molecule is engineered to bind with a protein found on the surface of cytotoxic T cells, and the other arm is designed to bind to a specific protein found primarily on tumor cells. 

When both targets are engaged, the BiTE® antibody construct is designed to form a bridge between the cytotoxic T cell and the tumor cell, which enables the T cell to recognize the tumor cell and fight it through an infusion of toxic molecules. The tumor-binding arm of the molecule can be altered to create different BiTE® antibody constructs  that target different types of cancer.

During the long drug discovery and development process, it is easy to forget who initially came up with the original idea. “That is why this year Amgen established the David L. Lacey Award to recognize those scientists who have made a significant contribution to science and medicine,” said Sasha Kamb, senior vice president of Discovery Research at Amgen.

The award is named after David Lacey, who led Discovery Research at Amgen from 2006 to 2011. During his 17-year career at Amgen, Lacey was responsible for a number of important innovations that led to approved medicines.

From Academia to Industry

Kufer was interested in science from an early age, initially the physical sciences. But after he finished high school, he felt he should focus more on biosciences or medicine. As a result, he started studying medicine at the University of Munich, and after a few years realized that immunology was the area where he wanted to focus.

“At the time immunology was not an area of study for medical students in Germany,” explained Kufer. “At one point, I was sitting together with biology students attending their immunology lessons which convinced me that I should do some laboratory work in that area. So I approached the head of Munich University’s Institute of Immunology and convinced him to take me as a student to do laboratory work in his institute.”

Kufer ended up studying medicine and working in the lab at the university, which proved to be a useful combination of skills. “When I finished my medical studies there, I was already very familiar with the subject of immunology. That gave me the opportunity, when I was starting full time work at the Institute, to get a small working group together.”

At the institute, Kufer assembled a small working group who, from 1991 to 1994, explored various approaches to developing bispecific T cell engagers, which eventually yielded a result.

“The BiTE® platform as such was born in 1994,” said Kufer. “I had my first talk at a scientific conference in December 1994 when I presented the first BiTE® ever at the Antibody Engineering Conference in California.”

But it wasn’t all smooth sailing. Other people were also interested in this technology and working at developing their own versions of bispecific antibodies.

“Around the time there was a very lively scientific community around the topic of bispecific antibodies,” said Kufer. “There were different formats of bispecific antibodies. But nobody knew yet how to best combine those two arms and what the best format was.”

“It is important to have these two arms combined in the right format so that the resulting bispecific molecule can efficiently serve as adaptor for T cells to recognize tumor cells which are otherwise hardly visible to them,” explained Kufer. One arm of the BiTE® is designed to identify B cells, including malignant B cells, while the other arm attaches to a T cell. This allows the T cell to see and attack the B cells.

Kufer continued working at the University of Munich until 2005, when he joined Micromet, a Munich-based company that developed BiTE® antibody constructs, on a full time basis. In 2012, Amgen acquired Micromet (now known as ARM) the same year Kufer was made a full professor at the Medical Faculty of the University of Munich. In April of 2015, Kufer was promoted to site head of ARM.

There are a number of BiTE® antibody constructs that are currently in development, and drug discovery scientists at Amgen are investigating ways to further enhance the structure and function of these molecules. “One area we are looking at is adding a half-life extension moiety [part of a molecule], which would make the BiTE® longer lived in the body,” said Kufer.

Becoming a Successful Drug Discovery Scientist

The question often comes up: what makes a good drug discovery scientist?

“Staying with it in difficult times,” said Kufer. “It’s always easy if you have sunshine and everything is fine. The difference is whether you cope with the difficult phases.”

This echoes David Lacey’s advice to aspiring “drug hunters,” as drug discovery scientists are often called.

“Follow your nose; sell others to get them to join you; take risks, sometimes big ones; ignore the naysayers provided they are not your boss, in this case, sell your boss,” said Lacey.

Looking to the future, Lacey believes there are great opportunities to make a difference to human health “if you only think expansively.”

“With the current tools available and the availability of breaking technologies,” explained Lacey, “the major limitations to successful innovation are those that are self-imposed.”