Horst Lindhofer: Musical cancer fighter
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- Before his career as a scientist and company founder, Horst Lindhofer attempted to forge a life in music. His biggest hit "Pogo in Togo" stormed the charts in the 80s. Source: Lindhofer
20.02.2009 -
Horst Lindhofer reached the top of the charts with his band "United Balls", before becoming a leading antibody researcher. He now develops cancer drugs that employ the body’s own immune system - and with great success. The European approval authority, EMEA, recently gave the green light for Lindhofer’s antibody drug, which has now cleared the largest hurdle before market entrance.
It is shortly before the founding of his company Trion Pharma in 1998, and the biologist Horst Lindhofer is beginning testing of his novel drug in the clinic. Previously, he has only been able to witness in mice how effective the substance is against cancer. One of his first patients is a former associate. Lindhofer has worked for some years in the laboratory alongside the technical assistant, but ovarian cancer has forced her to abandon her work. By now, the former colleague is in the last stages of the disease, with fluid accumulating continually in her abdomen, and doctors predicting an imminent death.
"There, I had a chance to see how difficult it is on the psyche of the patient to be faced with such a hopeless situation," recalls Lindhofer. She was administered with the new drug in hospital. She soon began to feel better, and fluids stopped accumulating in her abdomen. "We were happy that we could at least markedly improve her quality of life over a period of months, but unfortunately we were too late." She died not long after. "You should not wait to long before using our drug - at some point the immune system is unable to turn things around," says the biologist.
Working with the immune system
Lindhofer hopes that his approach will solve a fundamental problem associated with cancer therapies. "While many chemotherapies fight cancer, they also damage the immune system," says Lindhofer. In reality, the immune system is naturally responsible for fighting the disease in the body. This means that doctors are often faced with the dilemma of having to calculate whether the cancer or the treatment will be the first to kill the patient.
Lindhofer is convinced by his new method: The drug has already passed all clinical phases required for approval. "The special thing about our method is that we work with the immune system and not against it," asserts Lindhofer. Theoretically, it is even possible for the new drug to provide immunity against a specific cancer. A person can only fall ill with a particular type of flu a single time, because the immune system remembers the pathogen. If the system can then launch an effective attack, that person is immune. Likewise, the immune system could learn to remember cancer cells, and subsequently combat the metastases.
Novel antibody
The idea behind the therapy is to force the cells in the immune system to fight the cancer cells. To do this, Lindhofer has modified an antibody so that the substance is able to bind to three different types of cell: to a cancer cell, and two different types of immune cells, T-cells and macrophages.
"T-cells are highly potent killers, but are not so easily activated, otherwise they would go on to kill indiscriminately in the body," says Lindhofer. In order to begin work, they require two separate signals. One of these comes straight from the new drug. Macrophages play an important role in regulating the immune system. Because they also bind to the T cells as a result of the new drug, they provide the second signal.
The T-cells begin to kill cancer cells, thus encouraging the macrophages to activate more cells. In such a way, the new drug aligns the entire immune system against the cancer, as the active T-cells and macrophages recruit further useful cells. Ideally, a resistance to the cancer cells emerges.
Trial and error in the lab results in discovery
Lindhofer was originally led to this idea of developing antibodies that can bind to different cells 15 years ago by his then supervisor, Stefan Thierfelder. Lindhofer had just finished his doctoral studies on the AIDS virus and had begun a postdoctoral position at the Munich GSF Institute for Immunology. At the time, his supervisor told him to: “produce me some bispecific antibodies,” so Lindhofer started to try out some ideas in the laboratory. All antibodies are shaped like a Y, with a single stem and two smaller arms. These arms are normally identical, so that a maximum of two different kinds of cell can bind to the antibody; to the trunk and to the arms. After many unsuccessful attempts, Lindhofer finally succeeded for the first time in producing antibodies in large quantities that have two varying arms, and that can even bind to three different types of cells, because the stem of the Y can also bind to macrophages.
"No researcher will forget the moment when, after months of frustration, you finally achieve a result", remembers Lindhofer, referring to the moment when he realised he had successfully created the antibody. This moment was 15 years ago, and defines the work of the researcher still today. He initially presented his findings at a scientific conference, before he and his institute recognised the economic potential of his discovery. He then applied for a patent, before founding his company Trion Pharma a few years later. Financially, he was supported 100 percent by the pharmaceutical company Fresenius AG, which now owns a part of the company.
The musical biologist
Before his biology studies, and after school and military service, Lindhofer had staked on a very different career. Despite the awful name, he stormed the charts in 1981 with his ‘New German Wave' band United Balls. The hit "Pogo in Togo" can still be found today on a number of Greatest Hits of the 80’s collections. "But then I realised that I wasn’t talented enough to be able to only make music," recalls the scientist. So, he chose to study electrical engineering, but this was "too abstract," and he soon switched to biology. "I wanted to work on something that has a benefit."
The anticipated benefits could now come in the form of his new cancer drug. In the meantime, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency EMEA has given the go-ahead for approval of the drug. It could now be ready at the end of April 2009 - the first antibody on the market to be discovered and developed in Germany. With its approximately 100 employees, Trion Pharma would thereby have gone where no other German biotechnology company gone before.
Author: Ragnar Vogt
