Dr. Elisa Kieback says, for about a year, she has felt like “she’s on a rocket launch pad.” In 2015, the now 40-year-old researcher and entrepreneur teamed up with Professor Thomas Blankenstein of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and Holger Specht, Investment Director at IBB Beteiligungsgesellschaft, to found T-knife as a spin-off from the MDC and Charité. This leap from science to business was preceded by almost 20 years of basic research at the MDC – that’s how long Blankenstein has been working to realize his vision of curing cancer with the help of genetically modified immune cells, known as T cells.
For about ten years Blankenstein carried the idea of a spin-off around with him. He met Elisa Kieback in 2004 when he served as the second examiner for her doctoral thesis. “She is an exceptionally intelligent, motivated, organized and hard-working young scientist who has dedicated herself to T-cell receptor (TCR) gene therapy,” is how Blankenstein describes his co-founder. In 2015, the biologist moved from Professor Wolfgang Uckert’s lab to Blankenstein’s team and coordinated the first clinical trial on TCR gene therapy, which began in January this year at Charité –Universitätsmedizin Berlin. “When she learned that I was planning a spin-off from the MDC, she was eager to be part of it. I immediately agreed, and it is a decision I’ll never regret,” Blankenstein recalls. The name T-knife is as old as the founding idea itself. It is derived from genetically modified T cells – cells of the immune system – that are designed to cut tumors from healthy tissue much like a precision surgical knife.
T cells protect the human body from diseases such as viral infections. Infected cells can be recognized by the viral antigens that appear as typical markers on their surface. If a T cell detects an antigen with the help of its receptor, it either destroys the affected cell or triggers a wider immune response. Cancer cells also have special antigens on their surface, but the problem is that the immune system often does not recognize them as malignant and therefore does not fight them.
Thomas Blankenstein has devised a way to teach T cells to identify cancer cells as invaders and destroy them. He achieved this by engineering a genetically modified mouse with a human T-cell receptor repertoire. “When this transgenic mouse is injected with a human antigen that is foreign to the mouse, the mouse’s body mobilizes its defenses against the unknown antigen,” explains Blankenstein. “It starts to produce only T cells with matching receptors, which can then be easily isolated.” The idea: These highly specific T-cell receptors, which cannot usually be obtained from humans, are introduced into the patients’ T cells by gene transfer. This enables the patient’s own T cells to seek out cancer cells. If they are then infused into the patients, they can find and attack cancer cells.
This idea of a new immunotherapy against cancer is currently being tested on patients for the first time in a clinical trial at Charité – Universitätsmedizin Berlin. Within the next two years, a total of twelve patients with multiple myeloma, one of the most common cancers affecting bone marrow, will receive an infusion of their own T cells. These will be genetically modified beforehand so that their receptors recognize the antigen MAGE1, which is often located on the surface of multiple myeloma cells. This allows the T cells to do their job and kill the cancer cells.
The cell products for the entire study are being manufactured at the GMP Facility for Cellular Therapies at the Clinical Research Center (ECRC), a facility that specializes in the production of cell and gene therapeutics in clean rooms. The ECRC is a joint institution of the MDC and Charité.
Best-funded start-up in Germany’s biotech sector
Until 2018 T-knife existed only on paper. “Setting up the company as a joint venture was important because it allowed us to take the first organizational steps, such as hiring a law firm,” says Kieback. Then the founders converted T-knife into a limited liability company, Holger Specht dropped out and the technology transfer company Ascenion stepped in. The venture capital firms Boehringer Ingelheim and Andera Partners provided €8 million in initial financing. This enabled Kieback to hire a team of 15 employees and set up the first independent offices and labs on the Berlin-Buch campus. In 2020, she launched a second round of financing and raised an impressive €66 million – again from Andera Partners and Boehringer Ingelheim but also from US-based venture capitalists Versant Ventures and RA Capital Management. That made T-knife the best-funded start-up to date in the German biotech sector. She also brought Thomas Soloway on board as chief executive officer and Camille Landis as chief financial officer. Kieback herself is chief technology officer, which means she oversees product and platform development, while Blankenstein sits on the supervisory board.
There has been no stopping T-knife ever since. Being well-funded enables Kieback and her team to search for more TCR candidates to fight different types of cancer. The researchers have discovered several promising antigens that appear in tumors. “We will now produce and test suitable receptors,” says Kieback. Yet the 450-square-meter-space that T-knife moved into on the Berlin-Buch campus is starting to get cramped. At the end of 2020, 20 people were working there. That number grew to 40 by the first half of 2021. “The number will double again by the end of this year,” Kieback estimates. Besides, T-knife is opening a new office in Berlin-Mitte for the team responsible for clinical trials.
Off to the U.S. – and around the globe
T-knife has also set up a presence in the biotech stronghold of San Francisco. For one thing, most of the capital invested in T-knife comes from the United States. “If we want to take a long-term view and position ourselves well for further rounds of funding or for an IPO, then we have to be attractive to U.S. investors,” Kieback explains. For another thing, she is seeking to conduct clinical trials in U.S. hospitals. “The United States currently has more scientific expertise in advancing T-cell therapies into clinical trials compared to Germany,” she adds. Last but not least, Kieback hopes this move will lead to faster approval and quicker access to the U.S. market.
But that doesn’t mean she’s turning her back on Germany. “Berlin has a lot going for it as a science city,” Kienback enthuses, adding that the numerous universities and research institutes and the research hospital Charité produce many researchers that T-knife can recruit. San Francisco, she says, is the key to breaking into the U.S. market – but Kieback wants to enter the global market.
A unique technology with huge potential
She is confident this goal can be achieved. “The technology Thomas Blankenstein developed is unique,” she explains confidently. “Even people without a background in biotech recognize very quickly that it’s something very special and novel – with great potential both medically and economically.” It was this fact, Kieback says, that enabled her to win over investors. She also knows it would have been impossible without the large injection of money. “This form of therapy is very capital-intensive,” she explains. The German Federal Ministry of Education and Research provided €4 million in funding for the clinical trial that she got up and running at Charité. “That seems like a lot, and it’s great support,” she says. “But in the field of cell therapeutics, that amount doesn’t go very far if you want to develop a real product that will benefit a large number of people.” The clinical trial, the monitoring, the production of the patient-specific cell products – that’s completely new territory and extremely costly. “Because of the need to raise money for further development,” she says, “we had no choice but to start the company.” Financing is now in place until 2023.
Inventors need entrepreneurs
Kieback is totally comfortable in her new role as an entrepreneur. She is also convinced that the research world “needs to be more open to the fact that entrepreneurship is necessary if inventions are to make the leap from research to practice.” Besides, she continues to do research, albeit with a different focus: away from basic research, which formed the basis, and towards new product candidates and ultimately new therapeutics.
She has always wanted to go into research, so she decided to study biology in Heidelberg after finishing her Abitur. After an Erasmus year in Scotland, Kieback wrote her thesis at the German Cancer Research Center (DKFZ). In 2004, she applied for the PhD program at the MDC in Uckert’s research group on cellular gene therapy. “Gene therapy absolutely fascinated me,” she says. “Back in the 2000s, there was a lot of hype about the possibility of curing diseases by fixing broken genes and inserting new genes into cells. That’s what I wanted to do.” For her doctoral work, she developed a sort of safety switch that can stop cell and gene therapy if there are any unwanted side effects.
A role model for women in science and business
At some point she decided explore new career paths, leading her to apply for a study coordinator position in Blankenstein’s research group. “It was an all-around job and had the great advantage of providing a glimpse into many areas,” she recalls. When she heard of Blankenstein’s spin-off plans, she was immediately excited and eager to get on board. She enjoys building teams, identifying strengths and weaknesses, and encouraging and supporting people in their careers. One thing is very important to her: “Being a role model for women in science and business. I never thought I’d care about this, but my experience at T-knife has shown me how much it matters.” She is also keen to find out if the T-knife technology really works for patients. That is something only clinical data will tell. “We are committed to creating the best possible conditions for testing our platform in an optimal way. That’s what’s been driving me,” she stresses.
The breathtaking pace at which T-knife is growing requires constant change. You need a good amount of perseverance. Kieback admits that it is not always easy to manage if the number of employees doubles – from 20 to 40 – in a short time . “But I’m someone who thrives more on activity than stagnation. I become frustrated when things stand still,” she says, laughing a little.
There is no question of standing still for the time being. In July she will give birth to her second child. But if things do indeed slow down a little next year, she hopes to find time again for her hobby, dancing. It is a fitting pastime as it combines hard work with agility and lightness of foot.
Text: Jana Ehrhardt-Joswig