The Antibody Engineer

For his doctoral thesis, Jonathan Kiefer manufactured antibodies that help the body’s own immune system to defend against leukaemia cells. With a Pioneer Fellowship from ETH Zurich, he now plans to make his dream a reality: further develop the molecules – and bring the therapy to market.
Jonathan Kiefer is developing a therapy against leukaemia (Photograph: Kilian Kessler)

Acute myeloid leukaemia (AML) is a malignant cancer of the blood in which stem cells in bone marrow grow abnormally, producing only huge numbers of immature blood cells instead of healthy ones. “The most successful treatment at the moment is a stem cell transplant,” says Jonathan Kiefer, who has been a Pioneer Fellow at ETH Zurich since early this year.

Making treatment available to older patients, too

Before a patient can receive a stem cell transplant, their entire haematopoietic system (which is responsible for producing blood cells) has to be destroyed. Normally this is done with intensive chemotherapy. “However, this chemotherapy is highly toxic and has severe side effects,” Kiefer explains. For this reason, stem cell transplants are an option only for a minority of young, physically robust patients. “With the antibodies we’ve created, we want to make stem cell transplants available to the majority of older patients as well,” Kiefer says.

Using engineered molecules – Kiefer talks about “antibody building” – the researchers aim to instruct the immune system how to counteract the leukaemia cells. “We describe our antibodies as ‘bispecific’, because they can bind to two things at once,” Kiefer explains. The antibodies detect surface proteins on the blood stem cells affected by the leukaemia and on certain immune cells: the cytotoxic T cells. These protect the human body by destroying and eliminating sick cells. Once the bispecific antibodies have occupied both their binding sites, they form a bridge between the leukaemia and defence cells, thus demonstrating to the latter which cells they should be attacking.

“Always searching for the real-​life application”

“Our immunotherapy approach is much more targeted than intensive chemotherapy,” Kiefer explains. “If it proves itself in clinical trials, then in the future we could perform roughly 150,000 stem cell transplants globally instead of the current figure of 50,000. In other words, three times as many patients as today would have a chance at recovery.” This goal still lies a long way off, however. “It will probably still be a couple of years before we can test the antibodies on people,” Kiefer predicts.

The 31-year-old biotechnologist was born and raised in Munich. While studying for his Bachelor’s degree in Heidelberg, he gained his first practical experience in the lab at the German Cancer Research Center. His focus was on antibodies even then. “I’ve always searched for the connection to real-life application,” Kiefer says.

When it was time for his Master’s degree studies, Kiefer chose ETH Zurich based on its good reputation. After a brief research visit to MIT in Boston, he came back to ETH Zurich for his doctorate, where, as part of Professor Dario Neri’s research group at the Institute of Pharmaceutical Sciences (IPW), he developed his bispecific antibodies.

Pausing work in the lab

While working on his doctorate, Kiefer collaborated closely with the team under Markus Manz from the University Hospital Zurich. He now aims to use his Pioneer Fellowship to resume this successful collaboration. Pioneer Fellowships support individuals who want to found a spin-off with a salary and a well-equipped workspace for 18 months. The fellowship program also includes training and business courses as well as coaching from experienced entrepreneurs.

Kiefer started his fellowship this past February, but coronavirus measures forced him to stop his work in the lab relatively soon after. “I’m using the time to fine-tune my business case and to reach out to venture capital companies about follow-up funding,” Kiefer says.

Developing a new medication has always been a dream of Kiefer’s. He knows that the chances of success are slim: out of the numerous biotech start-ups, only a few manage to actually bring a new therapy to market. But he also knows that he can count on the support of his mentors, Neri and Manz. “This puts me in an excellent position to go about creating a company,” Kiefer says. Facing the manifold uncertainties on the path to commercial success calls for courage.

For Kiefer, one thing is clear: “The molecule deserves a chance to be developed further. These antibodies have the potential to revolutionise the standard of therapy for acute myeloid leukaemia, and they may also be useful in other areas of regenerative medicine,” he says.