Jacco van Rheenen
Group leader
Taxanes seem to ensure that the immune cells secrete vesicles that are poisonous to cancer cells.
Immune cells (T cells) freeze after treatment with taxanes, releasing vesicles that are toxic to cancer cells.
Interesting discovery
Ten years ago, he started investigating taxanes again. Together with group leader Rene Medema, he witnessed taxanes killing cancer cells in the described way on slides in the lab. But to their surprise, they didn’t observe the same effect in cancer cells in mice. The cells did die, but not because they got stuck in DNA division.
After moving his research group to the Netherlands Cancer Institute, he discovered something else together with medical oncologist Sabine Linn. Patients with many immune cells in their tumors responded much better to the taxanes than other patients. In his experiments, he observed that mice without these immune cells, known as T cells, did not respond to the chemotherapy. “The main question became: why is that?”
Poisonous vesicles
After many more experiments, he found his answer. “Taxanes seem to ensure that the immune cells secrete vesicles that are poisonous to cancer cells.” So the chemotherapy appears to activate the immune system to destroy the cancer cells. “And the best part is that these vesicles do kill the cancer cells but don’t harm the healthy cells.”
This new knowledge allowed them to provide a surprisingly effective treatment to mice with triple-negative breast cancer. Jacco: “We provided taxanes to the immune cells of these animals outside their bodies. Then we returned the cells to the mice. I was surprised by the results: I watched the tumors disappear entirely. That’s pretty amazing. This increases the efficacy of taxanes, without as many side effects because you only treat the immune cells outside the body.”
Breast cancer organoids (blue) dying (purple) by taxane-stimulated immune cells (T cells)
Living organisms
The first results in human cells and tissues in the lab seem promising. “We will be removing immune cells from human tumors, treating them with taxanes, and administering them to organoids – pieces of patient tissue in the lab. If that works well, we can start testing in patients. And most importantly, we want to have a greater understanding of how this works. What do these vesicles contain? How is it possible that these immune cells we return are so powerful? And are we overlooking any potential side effects?”
This study confirms how important it is to figure out how medicines work in living organisms. “Investigating living tissue is much harder and slower than loose cells in the lab,” Jacco explains. “That’s why scientists eventually still tend to opt for cells.”
Conclusive story
This discovery also shows that providing research and care under the same roof can really make a difference. Jacco: “Sabine and I work in the same department. Without her, I would never have been able to study cells from patients.”
Sabine: “His research into mice provided me with enough information to support a conclusive story and better acceptance of my findings in patients.”