How BLINCYTO Is Taking a BiTE ® Out of Cancer
Amgen’s BLINCYTO is a prescription medicine used to treat a certain type of acute lymphoblastic leukemia (ALL)—a cancer of the blood in which a particular kind of white blood cell is growing out of control. Dr. Peter Kufer, Executive Director, BiTE® Technology at Amgen, led the academic research group that innovated the BiTE® (i.e., bispecific T cell engager) technology behind BLINCYTO and—in collaboration with the academic research group of Dr. Ralf Bargou—developed the CD19–BiTE® BLINCYTO. Both Dr. Kufer and Dr. Bargou will accept the Inventor of the Year Award on 6 December at the IPO Education Foundation’s annual Foundation Awards Dinner in Washington, DC, where they and the inventors of five other cutting-edge cancer treatments will be recognized.
Here, Dr. Kufer describes for Innovator Insights how BLINCYTO works and what his hopes are for the next 10 years of cancer research.
What is your background and what was your role in developing BLINCYTO?
My training on patents was learning by doing under pioneer conditions.
I studied medicine at the University of Munich, Germany and received my Ph.D. in immunology. I had the luck, very early in my career, to lead an academic research group at the University of Munich that was focused on new antibody-based therapeutic approaches against cancer. It was in December 1994 when we first presented the BiTE® technology at the IBC Antibody Engineering Conference in La Jolla, California. The BiTE® now available as an approved drug under the name BLINCYTO was also engineered in my academic group at the University of Munich in 1996. It was a collaboration project with the academic research group of Dr. Ralf Bargou, who is now director of the Comprehensive Cancer Center of the University of Wuerzburg, Germany and receives the Inventor of the Year Award together with me.
I joined Amgen in 2012 through the acquisition of the German Biotech company, Micromet, founded in the 1990s as a spin-off of the University of Munich. At Amgen my role is Executive Director, BiTE® Technology, as well as site head and managing director of Amgen’s R&D site in Munich, Germany (i.e., Amgen Research Munich, or ARM).
What does BiTE® do, in laymen’s terms, and how?
The BiTE® mode of action appears to be particularly powerful in eliminating a small tumor burden that is the source of cancer regrowth causing relapse.
As part of our immune system, T cells are most potent in searching and destroying dangerous cells in our body. Typically dangerous cells are either cells infected with a virus or cancer cells. While the natural search and destroy mechanism of T cells is highly efficient in eliminating virus-infected cells, it is less efficient in killing cancer cells. BiTE® molecules are protein molecules with two different binding arms. One arm recognizes a target structure on the surface of a cancer cell and the other arm binds to the CD3/TCR-complex on the surface of T cells, which naturally mediates the recognition of dangerous cells by T cells and triggers their destruction. BiTE® molecules are designed to act as bridges allowing T cells to specifically recognize cells carrying certain target structures on their surface as dangerous cells and destroy them. BiTE® molecules under development at Amgen are being studied to allow T cells to search and destroy the tumor cells in patients suffering from different types of cancers.
How is it a step forward for cancer treatment and an improvement over previous approaches?
The true challenge in cancer treatment is often not the therapy after first diagnosis, but frequent relapses despite successful first line treatment and in particular how to prevent them. The BiTE® mode of action appears to be particularly powerful in eliminating a small tumor burden that often remains in the body despite successful primary cancer treatment and is the source of cancer regrowth causing relapse. This is where I see the most promising contribution of BiTE® molecules to the cure of cancer.
About 80% of adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) can today achieve a complete remission by chemotherapy. The challenge is that many of these patients (roughly 50%) get a relapse of their leukemia, which is very difficult to treat. That’s where BLINCYTO adds new potent treatment options for patients.
What role have patents played in your work? Did you receive training on patents in school or during your career at any point?
As a scientist in applied immunology dedicated to the development of new antibody-based therapeutics against cancer, it was clear to me from the very beginning that patenting new promising compounds prior to scientific publication is the prerequisite for further drug development. However, in the 1990s there was no patenting support by the university. So I took the initiative myself and filed several patents with the support of external patent attorneys. So my training on patents was learning by doing during my academic time under pioneer conditions.
What are your hopes for the next decade or so of cancer treatment based on your success?
My hopes for the next decade are:
- that BiTE® molecules will prove substantial therapeutic benefit in various other types of cancer beyond ALL;
- that we are successful in maximizing the curative potential of BiTE® molecules; and
- that the combination of cancer immunotherapies such as checkpoint inhibitors with BiTE® molecules will trigger a quantum jump in cancer treatment.
What does receiving the award mean to you?
Receiving the award together with my co-inventor, Dr. Ralf Bargou, means a lot to me. I am very thankful and I feel very honored. Personally, I am very thankful that I had the opportunity to substantially contribute to the development of BLINCYTO and of the BiTE® Technology from the innovation at the university over such a long period of time up to these days, when I am still working on new BiTE® molecules at Amgen. There are so many talented people I want to thank who joined in on this long way and substantially contributed to the success of BLINCYTO and the BiTE® Technology. They are simply too many to mention them all by name. The best award for all of us is to see how BiTE® molecules can potentially help patients and save lives.
I also want to congratulate the other award winners. The awards are all well deserved. They all stand for breakthroughs in cancer immunotherapy and, especially in combination, bear the hope for true quantum jumps in cancer treatment.