Tag: cancer therapy

A superlative milestone

A superlative milestone

PSI spin-off Araris Biotech AG is being acquired by the multinational pharmaceutical company Taiho Pharmaceutical Co., Ltd. The total value of the deal comes to USD 1.14 billion – making Araris the first PSI spin-off to achieve the exclusive unicorn-level!

The deal includes an initial payment  of $400 million and milestone payments of a further $740 million, bringing the total deal size to $1.14 billion. Contract structures like this are typical for the acquisition of companies in the biotech sector. The term ‘unicorn’ is used in the business world to describe something very special: a start-up that has achieved a valuation of over 1 billion US dollars.

With this deal, the start-up Araris, which was spun out of the Paul Scherrer Institute PSI in 2019, will now be fully acquired by Taiho Pharmaceutical Co. The total value of this acquisition confirms the innovative potential of Araris’ therapeutic approach, which aims to improve the efficacy and tolerability of cancer therapies.

Araris Biotech AG develops novel antibody-drug conjugates (ADCs) for the targeted treatment of cancer. The company was founded by Philipp Spycher, building on research carried out at PSI’s Center for Radiopharmaceutical Sciences. Spycher developed a method that allows cytotoxic agents to be bound to antibodies more firmly than before. In this technology, the antibody delivers the drug specifically to the diseased tissue, where it destroys the tumour cells. This work led to several patent applications and PSI’s own funding programme “PSI Founder Fellowship” supported him as he refined his research and developed a business idea. The concept convinced notable investors. Hence, the acquisition is a huge success not only for Araris Biotech AG, but also for PSI.

The technology transfer team at PSI supported Spycher on his journey from “researcher to entrepreneur” and ultimately helped him set up the spin-off Araris Biotech AG. PSI promotes spin-offs and with them the commercialisation of know-how and technologies developed at PSI that benefit society in the form of new products or services. “Spin-off companies are of strategic importance to PSI, because they bring the know-how gathered here to the market very efficiently, increase the visibility of PSI and contribute to strengthening the Swiss economy,” says John Millard, Head of Technology Transfer at PSI. Successful spin-offs also strengthen the innovative power of the Canton of Aargau and create new jobs. 

Read more on PSI website

Image: Araris Biotech AG develops novel antibody-drug conjugates for the targeted treatment of cancer. Shown here: an antibody-drug conjugate attached to two active drugs. The Araris technology allows the two drugs (orange and blue) to be attached to the antibody (turquoise) simultaneously by means of the so-called linker (yellow).

Credit: Araris Biotech AG

Optimizing gold nanoparticles for better medical imaging, drug delivery, and cancer therapy

Optimizing gold nanoparticles for better medical imaging, drug delivery, and cancer therapy

Health care professionals use tiny particles of gold (nanoparticles) for a variety of medical applications — from diagnostic imaging to cancer treatment. Gold works well for these applications because it doesn’t cause adverse reactions inside the body, it doesn’t break down easily, and it’s easy to see on imaging tests.

Ontario researchers used the Canadian Light Source at the University of Saskatchewan to determine whether the size of gold nanoparticles affects how they interact with an amino acid called L-cysteine. L-cysteine plays a key role in many biological processes inside the human body. It can prevent gold nanoparticles from clumping together, which is important for ensuring medical treatments work properly. L-cysteine can form a strong bond with gold, which in turn enables it to more easily attach to specific targets, such as cancer cells.

Yolanda Hedberg, a professor of chemistry at Western University, says that while many different sizes of gold nanoparticles are used in medicine, little is known about how size affects their performance. “We’re trying to understand what they do in the body and where they go. It is important to know if the (gold) particle stays the same size, because each size has specific properties and you design the particle in this way, and then don’t want it to change in the human body.”

Using ultrabright synchrotron light — combined with other techniques — Hedberg and her team discovered that smaller gold nanoparticles (5 nanometer) bond more strongly with L-Cysteine than larger ones (10, 15, and 20 nm). For reference, a human hair is about 100,000 nm wide.

They also found that the smallest gold nanoparticles didn’t clump together as much when L-Cysteine was present. Clumping can negatively affect the effectiveness, stability, and safety of nanoparticles. “This shows they can maintain their size and properties in a biological environment,” says Hedberg.

Read more on CLS website

Bleomycin: cancer drug with a hidden flaw

Bleomycin: cancer drug with a hidden flaw

Scientists at the B23 beamline of the Diamond Light Source have used synchrotron light to make an important discovery about a common cancer therapy. Bleomycin is used to shrink a variety of tumours, but little is known about how this drug interacts with proteins in the bloodstream. The beamline scientists used synchrotron-grade circular dichroism to study how bleomycin interacts with two common blood proteins, one of which is normally elevated in people with cancer. Reporting in the International Journal of Molecular Sciences, they found that the drug bound more firmly to the protein elevated in cancer patients, suggesting there may be less of the free form available to elicit its therapeutic effect. On closer analysis, the team discovered that one of two variants of bleomycin binds more strongly to this protein than the other. They caution that the ratio of these two variants may need to be adjusted to improve the therapeutic benefit of this drug.

While screening compounds produced by bacteria in the 1960s, scientists made a serendipitous discovery. They stumbled upon a molecule called bleomycin with anticancer properties. Since then, this life-saving drug has been used to treat a variety of tumours from squamous cell carcinomas to lymphomas. The drug works by chopping up DNA in cancer cells, and this DNA-drug interaction has been characterised in the past. However, when bleomycin enters the bloodstream, it may interact with plasma proteins and less is known about how this impacts the drug’s effectiveness. Bleomycin shows promising outcomes when tested on cancer cells grown in the lab, but the serum extracts used in lab cultures have a different mix of proteins to the sera of cancer patients, so it’s worth exploring whether plasma proteins in patients could sequester the drug and reduce its effectiveness.

Beamline scientists at B23 were determined to explore this overlooked issue. Led by Rohanah Hussain, they harnessed ultraviolet light from synchrotron radiation to explore how the drug binds plasma proteins using a technique called circular dichroism.

Circular dichroism is the differential absorption of left- and right-circularly polarised ultraviolet light passing through a liquid solution containing biomolecules, in this case proteins with drugs The CD measurement is displayed as a curve (spectrum) of which shape reflects the architecture on  how the protein in solution is folded in helical, ribbon, turn and unordered segments.  Drug binding to protein can affect such a folding that is used to identify and quantify drug binding interaction, in this case bleomycin with the two major blood proteins. Another unique experiment carried out at B23 beamline is the use of the powerful synchrotron beamlight to irradiate multiple of times the protein-drug mixtures for photostability assessment, which varies depending upon the strength of the drug binding interactions.

Hussain explained:

The high photon flux available at the B23 beamline (Diamond Light Source) generated by synchrotron radiation is sufficient for disrupting the folding of biological macromolecules in a time scale of minutes to hours, providing a useful tool for accelerated photo-stability studies.

First, the team assessed whether Blenoxane®, a commercial preparation of bleomycin, could bind to two common plasma proteins: one was human serum albumin (HSA), an abundant serum protein that facilitates the delivery of drugs around the body through the bloodstream. The other was α1-acid glycoprotein (AGP), a protein produced by the liver in response to inflammation that is found in cancer patients at ten times the normal level.

To explore binding interactions with these two proteins, the team examined the circular dichroism curve for each protein across a spectrum of ultraviolet light, and then they observed whether addition of Blenoxane® altered the protein curve. Sizeable differences were observed with AGP, suggesting the drug binds and induced marked changes to the protein’s shape, but the curve didn’t shift for HSA. This doesn’t indicate that the drug doesn’t bind HSA, only that it doesn’t alter its shape upon interaction. The team adapted their circular dichroism experiments to confirm that Blenoxane® did bind to HSA by heating the sample to unfold (denature) the proteins’ architecture and then observing spectral changes with and without the drug present.

Read more on Diamond Light Source  website

Image: Rohanah Hussain is a Senior Beamline Scientist, working on the B23 beamline at Diamond