It’s not unusual for the allocation of a grant from the Netherlands Organisation for Scientific Research (NWO) to be a precursor for an European Research Council (ERC) grant. And this was also the case with Pharmaceutical Scientist Sabrina Oliveira. In 2012, an NWO Veni grant enabled her to demonstrate the potential of a localised treatment of cancer cells using a new approach of targeted photodynamic therapy (PDT). The PDT that is currently applied in the clinic involves injecting light-sensitive chemicals – photosensitizers, that are not only associating with tumour cells, into the blood. Light is subsequently used to activate the photosensitizer locally, which then destroys the tumour cells. Oliveira introduced a new form of targeted PDT by conjugating photosensitizers to nanobodies – very small antibody fragments - that attach specifically to tumour cells and rapidly penetrate deeper into the tumour. The ERC Starting Grant subsequently awarded to Oliveira will now enable her to refine this approach and do conduct testing on a larger scale. This will bring improved treatment of tumours in places that are difficult to operate upon (such as the head and neck regions) a step closer.
Oliveira is pleased with the grant. “Improving this approach is certainly worthwhile. In the existing application in the clinic, the photosensitizer remains in the body for a long time, which means that it’s also a long time before the light can be used to activate it for therapy, usually between 2-4 days.”. The light activation leads to reactive oxygen species that destroy the membrane of the tumour cells, causing them to die. “Over the years, others have employed conventional antibodies to target photosensitizers more specifically to tumour cells, however those also remain in the body for several days. The approach that I’m developing reduces this time to just a few hours. It also seems to be more effective, because the nanobodies are a tenth of the size of antibodies, and can therefore penetrate deeper into the tumour.” Oliveira developed the idea for this approach during her Postdoc work at the Cell Biology Division of the department of Biology. “We used nanobodies conjugated to fluorophores to detect tumours in mice via optical imaging. Compared to conventional antibodies, these accumulated more rapidly and distributed more homogenously.” But her ambitions extend much further. “I want to test whether, in addition to destroying the cancer cells in the tumour, the nanobody-targeted PDT can also destroy its vascular system and stem cells. And if they can, whether this can further increase the chances of complete cancer eradication. I also want to investigate if it is possible to activate the patient’s immune system during the process, so that it attacks the cancer, in case of recurrences.”
In order to further refine the approach , the researcher will conduct in vitro and in vivo tests on human cells implanted in mice over extended periods of time. Numerous nanobodies have already been developed and characterized and newer ones that bind to different targets will be selected at Utrecht University for use in the research.
Her researchers will also use the developed approach at the Faculty of Veterinary Medicine, on dogs with cancer for which options for treatment have been exhausted or are simply inexistent. Only if their owners grant permission, of course. “In the case of prostate cancer, for example, no real option for therapy exists, so we could try to make a difference for these animals, while learning whether this treatment will have a chance to work on spontaneously developed cancers in larger subjects. I think that this is the most exciting part of the research. If it works as we hope it will, perhaps other parties become interested and consider starting clinical trials on humans.”
Oliveira will be collaborating with numerous other Dutch researchers during the research. Within Utrecht University, she’ll primarily work with Cell Biologist Paul van Bergen en Henegouwen, with the group of Pharmaceutics and with the University Medical Center Utrecht. She’ll also be collaborating with the Erasmus Medical Center in Rotterdam, where researchers offer a wealth of expertise regarding light activation of photosensitizers. Oliveira is now a much sought-after researcher. On July 1st , she took up a joint position at Cell Biology and Pharmaceutics , where she’ll be conducting some of the tests. And the next step? “If this treatment is more effective, I’d like to extend the research further. In the future, perhaps we can use nanobodies to make more treatments really cancer specific.”