How genetic engineering can improve cancer drug efficacy

18 Jul 2023

Image: Cristina Abascal Ruiz

A quirk of genetics gave this PhD researcher a streak of white hair and the path to her career. Now, Cristina Abascal Ruiz is genetically engineering antibodies to improve treatments for cancer and other diseases.

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Cristina Abascal Ruiz is committed to disseminating scientific knowledge to wide audiences and makes a particular effort, through workshops and events such as Soapbox Science, to encourage young women to undertake STEM careers. She has been inspired by many women, but mentions Rosalind Franklin in particular, a pioneer in the discovery of the structure of DNA.

“The fact that her name was erased from history for a long time is a symbol of how the scientific contributions of women have been completely unknown due to patriarchal culture,” says Ruiz.

With an undergraduate degree in biotechnology and a master’s degree in molecular biology, Ruiz is now pursuing a PhD in bioengineering at University College Dublin. As part of her doctoral studies, she is involved with the Centre for Doctoral Training in Transformative Pharmaceutical Technologies, which is run in partnership between the Science Foundation Ireland Research Centre for Pharmaceuticals (SSPC), University of Nottingham and University College London.

Tell us about your current research.

Currently, I am working on the glycoengineering of monoclonal antibodies, which is an important aspect of biopharmaceutical production.

Monoclonal antibodies (mAbs) are laboratory-produced molecules which can serve as substitute antibodies to modify or mimic the immune system’s attack on unwanted cells. They are widely used in the treatment of cancers and autoimmune diseases, and their demand is increasing.

However, ensuring the quality and efficacy of mAbs remains a challenge. These antibodies are glycoproteins, and glycosylation plays a crucial role in their structure and function.

N-glycosylation, which involves adding carbohydrates to specific sites on the antibody, is the primary form of glycosylation in these antibodies. Understanding and manipulating glycosylation can help improve the homogeneity, safety and therapeutic effectiveness of mAbs.

For this aim, our research group is working with Chinese hamster ovary (CHO) cells. My PhD project focuses on maximising human sialylation (a glycosylation modification that helps the immune system distinguish between healthy and altered cells) and eliminating CHO-like sialylation.

This will lead to improvements in the product, imparting better anti-inflammatory and pharmacokinetic properties.

Why is your research important?

In the coming years, the need for antibodies will grow even more, so being able to produce them in the best conditions will be beneficial for both patients and the pharma industry.

The implementation of innovative approaches in biopharmaceutical manufacturing can have significant impacts.

Optimising sialylation patterns enhances the quality of biopharmaceuticals, improving their functionality, efficacy and patient responses. It also influences the binding affinity of the antibodies, increasing selectivity and reducing off-target effects.

Manipulating the sialylation process also allows for better control in the manufacturing process of these antibodies. This ensures reproducibility, scalability and consistent production of the antibodies with the desired sialylation profiles, minimising process-related variations.

What inspired you to become a researcher?

Since I was a child, I have always loved science because I’m a very curious and creative person.

To pick out a specific moment, it was perhaps in a biology class at the age of 12. I was born with a streak of white in my hair (known as a ‘Mallen streak’), which is a genetic mutation called poliosis. I had never seen anyone in my family with it, and that day in that book where they were explaining basic concepts of Mendelian genetics and gene trees, there was a picture of a girl with the same streak as me.

From that moment on, I became fascinated with genetics and later with genetic engineering.

What are some of the biggest challenges or misconceptions you face as a researcher in your field?

Being a young woman in an engineering field is undeniably challenging. While it is true that in the Irish and European context, equal opportunities for education have been achieved through years of feminist and social movements, gender stereotypes and societal perceptions still contribute to the gender divide in many scientific areas.

Certain fields, like engineering, are predominantly influenced by these stereotypes, leading to the perception that women are not as serious nor intelligent enough.

Additionally, the burden of family responsibilities, which I personally do not experience currently, but witness in my peers, further exacerbates the situation. Unfortunately, the unequal distribution of responsibilities between women with dependent children and men creates a clear disparity in professional development and fosters inequality.

Do you think public engagement with science has changed in recent years?

Certainly, there has been increased societal awareness regarding the significance of scientific research. However, regrettably, it has also given rise to a plethora of misinformation and confusion surrounding certain concepts, notably vaccines.

Consequently, I believe it is crucial to dedicate time and effort to the dissemination of scientific knowledge, ensuring that society remains informed about the extensive work that underlies even seemingly common products like a box of paracetamol.

I actively engage in science communication events, adhering to the principle of ‘keeping it simple’. If you can effectively convey complex ideas in simple language that can be understood by your grandparents, then that signifies successful communication to me.

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