Nadia Mensali, Else Marit Inderberg and Sébastien Walchli, lead authors of the study named "Transient TCR-based T-cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer". Photo: Oslo Cancer Cluster.

Cell therapy breakthroughs in cancer treatment

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The Section for Cellular Therapy’s Translational Research Unit in Norway has recently published two groundbreaking studies demonstrating the potential of cell-based therapies in the fight against cancer. The research group used the Oslo Cancer Cluster Incubator labs to develop pre-clinical treatments.

The collaborative team from Oslo University Hospital and the University of Bergen have made significant progress towards developing more effective and targeted treatments for advanced and treatment-resistant cancers.

Tackling colorectal cancer resistance

The first study, titled “Transient TCR-based T-cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer,” focuses on a novel approach utilizing T-cell therapy to treat metastatic colorectal cancer. Published in a reputable journal, the study details the successful and safe application of a transient T-cell receptor (TCR) therapy named Radium-1 in a patient with advanced colorectal cancer resistant to conventional treatments. The therapy is named Radium-1, as it was discovered at the Radium Hospital (now part of Oslo University Hospital).

Dr Else Marit Inderberg, one of the lead researchers, explains the rationale behind their approach, stating,

“We aimed to modify the immune system to recognize and destroy tumour cells effectively. We transferred TCRs from responsive patients to non-responding ones, leading to promising results in our clinical trial.”

The therapy involves modifying a patient’s T cells to express the Radium-1 TCR using messenger RNA (mRNA) technology. Despite the challenging nature of advanced colorectal cancer, the treatment was well tolerated by the patient and resulted in stable disease, offering hope for further investigation in larger clinical trials.

Breakthroughs in ovarian cancer treatment

The second study, titled “Efficient CAR T cell targeting of the CA125 extracellular repeat domain of MUC16,” introduces a novel Chimeric Antigen Receptor (CAR) T-cell therapy targeting ovarian cancer. Ovarian cancer remains a significant challenge due to late-stage diagnosis and chemoresistance, making the development of new therapeutic strategies imperative.

Co-author Christopher Forcados and lead author Nicholas P. Casey. Photo: Oslo Cancer Cluster

Dr Nicholas P. Casey, the lead author of the study, emphasizes the importance of their research, stating, “Our CAR T-cell therapy targeting the CA125 extracellular repeat domain of MUC16 shows promising efficacy in preclinical models, offering a potential breakthrough in ovarian cancer treatment.”

The CAR T-cell therapy has shown promising results in both in vitro experiments and patient-derived xenograft mouse models. This paves the way for future clinical trials aimed at advancing CAR T-cell therapy for ovarian cancer patients. The development of these therapies took place in the fully-equipped laboratories of Oslo Cancer Cluster Incubator, specifically designed for carrying out these processes.

New hope and results ahead

These pioneering studies highlight the transformative potential of cell-based therapies in revolutionising cancer treatment. With further research and clinical validation, these innovative approaches could offer new hope for patients battling advanced and treatment-resistant cancers, and getting closer to realizing the vision of personalized and targeted cancer therapy.

As Dr Sebastien Wälchli, co-author of the studies, fittingly summarizes, “These findings underscore the importance of collaborative research efforts in advancing cancer immunotherapy and signify a significant step forward in our ongoing battle against cancer.”

The research group is anticipating the publication of a third article, which is expected to contain groundbreaking results. Stay tuned for further updates.

What is T-cell therapy for colorectal cancer:

Imagine your body has soldiers called T cells. These cells can recognize and fight against harmful things like cancer cells. In this therapy, scientists take T-cells from a patient’s body. Then modify these T-cells in a lab to make them better at recognizing and attacking cancer cells. It’s done by giving the T-cells a special weapon called Radium-1.

However, these modified T cells don’t stay in the patient’s body permanently. Instead, they are given back to the patient temporarily. These modified T cells go on a mission to find and destroy cancer cells. Even though they’re only there briefly, they can still make a big impact in fighting cancer cells.

What is CAR T-Cell Therapy for Ovarian Cancer:

In this therapy, scientists create special T cells called CAR-T cells. These T-cells are trained to recognize a specific target on ovarian cancer cells called MUC16. These CAR-T cells are specifically designed to find ovarian cancer cells.

In simpler terms, both therapies involve giving the body’s immune system a boost to help fight cancer more effectively. It’s like giving the immune system an upgraded set of tools to target and destroy cancer cells.

 

The post Cell therapy breakthroughs in cancer treatment first appeared on Oslo Cancer Cluster.

Tor Haugen attended a work placement at Thermo Fisher Scientific, arranged by Oslo Cancer Cluster and Ullern Upper Secondary School, where he tried DNA profiling. Photo: Elisabeth Kirkeng Andersen

DNA profiling on the syllabus

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Tor takes a mouthswab before in order to profile his DNA.

Students learned about a Norwegian invention behind CAR T-cell therapy and DNA profiling on their latest work placement.

This article is also available in Norwegian here.

Thermo Fisher Scientific is a global company that develops the Norwegian technology, which is based on “Ugelstad-kulene” (The Ugelstad Beads). In June 2019, Einar, Tor, Olav and Philip from Ullern Upper Secondary School completed a work placement with Thermo Fisher Scientific in Oslo. They used the beads to profile their own DNA and learned how the beads can be used to find murderers, diagnose heart attacks and save children from cancer.

“What do you plan to study when you finish upper secondary school?” Marie asks.

“The natural sciences,” Einar and Tor replies.

“The natural sciences at NTNU,” Olav says.

“First, the natural sciences and then, join the Air Force,” Philip answers.

Marie Bosnes is supervising the students who are attending the work placement and has worked more than 24 years in the Norwegian section of Thermo Fisher Scientific. She conducts research and development in the former monastery located on Montebello, next to Oslo Cancer Cluster Innovation Park and Ullern Upper Secondary School.

Today, Marie and several of her co-workers have taken time out of their busy schedules to tutor the four students from Ullern: Einar Johannes Rye, Tor Haugen, Olav Bekken and Philip Horn Børge-Ask. The students have nearly finished their second year and have so far focused their studies on mathematics, physics, chemistry and biology. But next year, they will also study programming, instead of biology.

“It is a good mix of subjects, especially programming is useful to learn. You should consider studying bioinformatics, because, in the future, it will be a very desirable qualification,” Marie says.

Marie has studied biology and her co-workers call her Reodor Felgen (a character from a famous Norwegian children’s comic book), since she loves to constantly explore research on new topics.

Treating cancer

An ullern student is looking at the dynabeads in a test tube.

Philip Horn Børge-Ask looks at the test tubes that contain the famous “Ugelstad-kulene”. Photo: Elisabeth Kirkeng Andersen

While Einar, Tor, Olav and Philip are on a work placement with Marie, four other Ullern students are on another work placement with Thermo Fisher Scientific in Lillestrøm. This is where they develop and produce Dynabeads for the global market.

“Dynabeads are also kalled ‘Ugelstad-kulene’, because they are a Norwegian invention. During the ‘1970s, one of NASA’s goals was to make perfectly round and identical, tiny, plastic microbeads in outer space. No one thought it was possible to make them on Earth. John Ugelstad, a Norwegian chemical engineer, did not accept that fact. He completed several difficult calculations, which enabled him to produce these tiny beads on Earth,” Marie explains.

Thanks to the tiny beads, Thermo Fisher Scientific has experienced huge global success. Even though there are only 200 employees situated in Norway (out of 70 000 employees globally), the research and development conducted in Norway is extremely important for the whole company.

“We are proud to announce that every year Dynabeads are used in almost 5 billion diagnostic tests in the world,” Marie says.

Thermo Fisher Scientific has developed the beads further, so they can be used in CAR T-cell therapy to treat cancer. The first approved CAR T-cell therapy in the world that treats child leukaemia was approved in Norway in December 2018. The advanced technology is based on the Norwegian invention “Ugelstad-kulene”.

  • Watch the video from the Norwegian TV channel TV2 about Emily Whitehead, the first child in the world that received this CAR T-cell therapy. She visited Thermo Fisher Scientific in Oslo in March 2019.

Catching killers

Elisabeth and Mary are supervising the students in the lab

Elisabeth Breivold and Marie Bosness from Thermo Fisher Scientific supervised the students in the lab. Photo: Elisabeth Kirkeng Andersen

“The beads are used for many different purposes and you will learn about a few of them today. Simply put, the beads are like a fishing rod. Depending on which bait you fix to it, the rod can be used in different ways,” Marie says. “Before lunch, we will use Dynabeads for DNA profiling. This technology is commonly used by police to identify suspects after a crime, just like in the TV series CSI.”

During the presentation, Marie shows the students the front page of an American newspaper with a mugshot of Gary Ridgway, an American serial killer, also known as “The Green River Killer”. Ridgway has now confessed to killing 71 women. For many years, the police hunted the murderer without any luck. Finally, new technology enabled the police to retrieve damning evidence from the tiny amounts of DNA that Ridgway had left on his victims. The DNA evidence led to a successful conviction of the killer.

“The DNA evidence was established with DNA profiling, using Thermo Fisher Scientific’s products. They did not use Dynabeads back then, but today, they would have used the beads. You will learn how to do it yourselves in the lab,” Marie says.

Learning to profile DNA

Olav takes the mouth swab

Olav performs a mouth swab on himself, the first step to retrieve the DNA. Photo: Elisabeth Kirkeng Andersen

Before the students enter the laboratory, they need to put on protective glasses, lab coats and plastic shoe covers. The students will profile their own DNA, the same way the police profile the DNA from suspects or criminals.

First, the Ullern students collect the cells with a mouth swab. Then, they add the different enzymes and chemicals that will open the cell membranes into the test tube, so that the DNA is released.

Afterwards, the Ullern students add “Ugelstad-kulene”, which bind to the DNA like magnets. Then, they retrieve their DNA from the solution.

They put the DNA in a kind of “photocopier”, in order to study it with something called “gel electrophoresis”. This is a method for analysing individual parts of DNA that make up the human genome. It shows a bar code pattern, which is completely unique for every person in the world.

Tor is using the pipette in the lab.

Tor adds new chemicals to the solution with his DNA. Photo: Elisabeth Kirkeng Andersen

“DNA is incredibly stable, which means that we can retrieve it from people and animals that died a long time ago and copy their DNA so that it can be analysed,” Marie explains.

“The most fun was to retrieve our own DNA. We tried it ourselves and it was fun to learn how to do it,” Philip says.

The Ullern students were very happy with their work placement at Thermo Fisher Scientific.

“I think the placement was educational and interesting. It was very well arranged and we got to try many different things. What surprised me the most was probably the close collaboration between scientists at Thermo Fisher Scientific – it seemed like everyone knew each other!” Philips says at the end of the day.

After the students had completed the DNA profiling, they ate lunch and then they learned more about the use of “Ugelstad-kulene” in diagnostics, and CAR T-cell therapy.

Elisabeth Breivold supervised the students while they performed the DNA profiling in the laboratory at Thermo Fisher Scientific.

Elisabeth Breivold supervised the students while they performed the DNA profiling in the laboratory at Thermo Fisher Scientific. Photo: Elisabeth Kirkeng Andersen

 

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