Researcher’s Chronicle | From Oeiras to Stockholm: João Jacinto Investigates the Potential of NK Cells to Develop New Cancer Immunotherapies

Researcher’s Chronicle | João Jacinto – Karolinska Institutet, Stockholm

Every day, cells with the potential to become cancerous emerge in our bodies. Fortunately, our immune system has mechanisms capable of recognising and eliminating them. These natural defence mechanisms have inspired the development of immunotherapy, an approach that seeks to harness the body’s own immune system to fight cancer.

What Are NK Cells?

Among the immune system’s defence mechanisms are Natural Killer (NK) cells, a type of white blood cell involved in the early immune response against viral infections and tumour cells.

One of the remarkable abilities of these cells is that they do not need to “learn” what a cancer cell is before attacking it. They patrol our bodies looking for abnormal signals or signs of cellular stress, attacking affected cells by releasing toxic granules and alerting other immune cells to potential threats.

These characteristics make NK cells particularly attractive for therapeutic applications in oncology, especially as an “off-the-shelf” treatment. This refers to a cell-based product that can be manufactured in advance, stored, and made immediately available to different patients, without requiring personalised production for each individual.

It was precisely the potential of these cells that motivated me to undertake a research internship at Karolinska Institutet (KI), in Sweden, in Dr. Evren Alici’s laboratory, supported by the SPOT Nordic Fellowship.

Currently, several strategies are being developed to harness the potential of NK cells and create more effective and safer treatments for different types of cancer. However, despite their enormous potential, significant challenges remain regarding the production, availability, and cost of these therapies.

From Stem Cells to NK Cells

NK cells are currently often obtained from peripheral blood or umbilical cord blood. However, these approaches depend on donor availability, are affected by variability between individuals, and present challenges in consistently producing large quantities of cells.

As an alternative, researchers have been exploring the possibility of generating NK cells from human induced pluripotent stem cells (hiPSCs).

hiPSCs are adult cells that have been reprogrammed into a state similar to embryonic stem cells, allowing them to generate virtually any cell type in the human body.

Compared with traditional sources, hiPSCs offer the possibility of producing large quantities of NK cells more consistently, establishing well-characterised cell banks, and facilitating the development of off-the-shelf therapies.

Beyond Cells: The Potential of Extracellular Vesicles

Another important focus of my project is the study of extracellular vesicles (EVs) produced by NK cells.

EVs are small particles naturally released by cells that carry proteins, lipids, and genetic material capable of influencing surrounding cells. They also function as a means of communication between cells.

In the case of NK cells, these vesicles can carry molecules with antitumour activity, reproducing some of the therapeutic effects of the cells from which they originate.

Interest in these EVs has been growing due to their easier storage, the possibility of developing cell-free therapies, and the reduction of certain risks associated with administering living cells.

For these reasons, many researchers believe that EVs could complement or, in certain contexts, replace cell-based therapies.

A Collaboration Between Portugal and Sweden

My PhD project, currently being developed at the Instituto de Biologia Experimental e Tecnológica (iBET), in Oeiras, Portugal, focuses precisely on developing an integrated, continuous, and scalable process for producing hiPSC-derived NK cells and purifying their corresponding EVs.

The ultimate goal is to contribute to the development of more efficient, safer, and more accessible immunotherapies for patients.

To achieve this objective, establishing an international collaboration that brought together complementary expertise became essential. It was in this context that the opportunity arose to undertake a research internship in Dr. Evren Alici’s laboratory, with the support of the SPOT Nordic Fellowship.

This work is the result of a collaboration between iBET and KI.

While KI has extensive expertise in NK cell biology, cancer immunotherapy, and translational research, iBET has developed strong capabilities in bioprocess engineering, cell production in bioreactors, and the development of scalable manufacturing processes for advanced therapies.

Combining these areas of expertise creates unique opportunities to accelerate the development of new therapeutic strategies.

Over six months, I had the opportunity to learn directly from researchers specialising in NK cells, deepening my knowledge of the processes involved in their differentiation, expansion, maturation, and characterisation, as well as the characterisation of their corresponding EVs.

The knowledge acquired will now be applied at iBET to support the development of more robust and scalable production platforms, helping to bring these therapies closer to their future clinical application.

My Experience at Karolinska Institutet

Although the scientific objectives of this collaboration were clear, the experience ultimately went far beyond laboratory work.

The months I spent at KI provided me with a unique perspective on international research, multidisciplinary collaboration, and the journey required to transform a scientific discovery into a potential therapeutic solution.

One of the most enriching aspects of the experience was observing firsthand how researchers from very different fields work together to address common challenges.

Within a single project, it was common to find specialists in immunology, cell biology, bioinformatics, and clinical medicine contributing different perspectives, demonstrating the importance of multidisciplinarity in modern biomedical research.

Another particularly interesting aspect was the strong integration between fundamental research, technological development, and clinical application at the Flemingsberg campus.

The proximity between laboratories, hospitals, and industry allowed me to gain a better understanding of the challenges involved in translating new therapies from the laboratory to patients.

This internship allowed me to return to Portugal with new scientific knowledge, a broader international collaboration network, and a more integrated perspective on the future of immunotherapy based on NK cells and EVs.

More than simply learning new techniques, this experience showed me the importance of international collaboration in biomedical research and reinforced my conviction that the most significant scientific advances often emerge when different fields of knowledge and different countries work together to address shared challenges.

Above all, it strengthened my motivation to continue developing strategies that can help make these therapies more effective, accessible, and available to patients.