Many chemotherapeutic drugs used in cancer treatment act on the patient’s normal cells as well as the cancerous ones. Developing a more specific, targeted approach for cancer treatment is the focus of Dr. Sabrina Santos Oliveira’s research. We talked to Dr. Oliveira, who is based at Utrecht University in the Netherlands, about the current status and future directions of her work.
AcademiaNet: Dr. Oliveira, in your research you focus on the “holy grail” of cancer treatment: effectively targeting cancer cells while leaving healthy cells unscathed. Can you briefly outline the approach you take?
Dr. Oliveira: The main approach I use is to chemically join (pro)drugs to very small antibodies (known as nanobodies or single domain antibodies) that are capable of binding very specifically to certain proteins present on the surface of cancer cells. Those proteins are sometimes also present on normal cells, but generally to a lower degree. This difference makes it possible to discriminate cancer cells from normal cells. In addition to this, one of the approaches I use makes use of light to activate the pro-drug and, as light is only locally applied, it also restricts the site where toxicity is produced. Thus, we can say that with nanobody-targeted photodynamic therapy (PDT), I make use of two combined aspects to effectively kill cancer cells, while leaving normal tissues unaffected.
Are there any specific molecules or indeed cancers for which you think your method is particularly suitable?
Nanobody-targeted PDT can in principle be applied to all cancers that are confined in their primary location, so not yet spread through the body. The application of light may require some assistance, but in principle any cavity of the body or organ can be illuminated, either directly exposed if combined with surgery, or by use of endoscopes and optical fibers. Our research is mostly done in head and neck cancer models and in breast cancer, but in the future, we would like to investigate other cancers.
Do you think that your approach might also be useful in the early diagnosis of cancer?
We have shown in laboratory animal experiments that nanobodies can be used as tracers for optical imaging. Others have obtained promising results in a phase 1 clinical trial using imaging based on radioisotopes. So yes, I think nanobodies could be used to complement current diagnostic tools. For instance, by assessing if a certain target is present in a patient we can decide whether a targeted therapy should or should not be given to the patient, or it can be used to assess if the patient is responding to the treatment.
Also, the photosensitizer we use is a fluorophore in the near-infrared range of light. This property means that we can first check where it accumulates and then (by changing the light to a more powerful laser) the photosensitizer can be activated for PDT.
The effectiveness of photodynamic therapy seems to rely upon robust immune responses directed against the invading tumor. Do you have any idea about how your nanobody-based approach engages the immune system?
We have just initiated this type of research and so far, we have indications that innate immunity is indeed triggered. We hope to extend this to other studies to have a whole overview of what this PDT does to the immune system.
Are you combining your nanobody-based photodynamic therapy with chemotherapeutic drugs or other anti-cancer treatments?
Not yet. But of course, this may happen in the future.
How far away do you think we are from potentially seeing nanobody-targeted photodynamic therapy in the clinic?
Well, the first nanobody for radioisotope-based imaging has been through phase I, and the photosensitizer we use is in a phase I trial conjugated to an antibody, so I hope that our research will contribute to the translation of this new approach to clinical research. It's hard to estimate when, but I hope we can reach a trial in the veterinary clinic in less than four years.
Thank you for this interesting interview, Dr. Oliveira!
Questions were asked by Neysan Donnelly for AcademiaNet and Spektrum.de.(© Neyson Donnelly / AcademiaNet / Spektrum.de)