With a 23-week pregnant belly, Lotte Eijkenboom (32) defended her dissertation in February. Doctor and mother. From an early age she knew that she wanted to be both equally. With a second child on the way and a PhD project behind her, this dream has come true. But the doctor in Eijkenboom knows better than anyone that she has been lucky. Getting pregnant is not easy for everyone.
She worked as a fertility doctor at the Radboud University Medical Center in Nijmegen for three and a half years. At her consultation hours she saw women who were unable to get pregnant for a variety of reasons. But also women who had not even thought about that big choice, and were told that they have cancer. “With such a diagnosis, your whole life is turned upside down,” says Eijkenboom. “Imagine that the oncologist immediately tells you that you need to see a gynecologist as soon as possible for a conversation about your desire to have children. That is very intense.”
Will the woman be asked whether she wants to have her eggs frozen, or even an embryo? In case the cancer treatment with chemotherapy or radiation will make her infertile. Sometimes the cancer is so aggressive that there is no time for that at all. Or the woman is still too young to donate her eggs through hormone treatment. In such a case, says Eijkenboom, you can freeze a piece of tissue from the bark of the ovary.
Replace safely
Eijkenboom has been conducting research into the latter, ovarian tissue, over the past four years. Hope of safe fertility restoration after cancer is called her thesis. Eijkenboom investigated how you can safely replace frozen ovarian tissue in a woman who has been cured of cancer. “If patients have tissue frozen, we cannot rule out that it also contains tumor cells,” Eijkenboom explains. She therefore looked for ways to clean the tissue outside the body: destroying the cancer cells, while protecting the eggs in the same tissue.
This is called purging. For some types of cancer it is known which substance is very suitable for destroying tumor cells. For example, verteporfin – a drug against eye diseases – works well against leukemia and rhabdomyosarcoma, a tumor in muscle tissue. Everolimus – a drug that suppresses immune responses – works against Ewing’s sarcoma, a form of bone cancer. “This way you can look for a specific medicine for each form of cancer,” says Eijkenboom.
But it can be even more precise, she discovered. By using so-called DARPins. These are very small proteins created in the laboratory, specifically designed to attack one type of membrane protein on a cell. In this case the tumor cell.
Destroy from within
“We can unravel the unique ‘code’ of some tumor cells, a kind of lock that only fits one specific key. We can then design a protein with a code that fits exactly into that slot. We attach a poison to that DARPin. The DARPin binds to the tumor cell, the poison goes in and destroys the cell from the inside.” Eijkenboom developed this method together with the biochemistry department. They already had the DARPin technology on the shelf there, but had not yet found a concrete application for it.
It almost sounds too good to be true, a drug that is so precise and effective. In a petri dish with tissue it works almost perfectly. This raises the question of whether we can also attack tumor cells in the body with such a DARPin. Eijkenboom is very clear, unfortunately that is not possible. “Yes, these proteins also do their work in the body, but there they provoke a strong immune response. Not only the tumor cells, but also the body’s own cells are attacked. You get a lot of side effects from that.”
Manually infecting with cancer
Ovarian tissue containing tumor cells for research purposes is rare, says Eijkenboom. That’s why she had to manually ‘infect’ healthy ovarian tissue with cancer. The ovaries she used came from transgender men who underwent gender reassignment surgery and donated their ovaries to science. She took the tissue out of the freezer, let it thaw and injected the tumor cells into the tissue with a very small, thin needle. “After a few days in culture you will automatically see the formation of metastases, small tumor islands.”
There has not yet been a huge medical breakthrough, Eijkenboom emphasizes. The results of her research are promising, but according to her, we are still a long way from being clinically applicable. “We now know that we can eliminate cancer cells in a petri dish. But what we don’t know yet is how the body will react when we replace this cleaned tissue.”
Transfer to mice, then perhaps to monkeys, can tell us whether the ovarian tissue produces healthy offspring. And you want to know whether the tissue can produce mature egg cells that show no abnormalities. “Based on my results, we assume that the products we use have no effect on offspring, but we have to prove it first. If we succeed, we will indeed have something very nice.”
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