Made-in-Toronto cancer nanomedicine receives green light for clinical trial

A team of Toronto researchers has received Health Canada approval to conduct clinical trials for a novel class of nanoparticles that could improve cancer detection diagnosis – 14 years after the nanoparticles were first discovered.

The nanoparticles, called porphysomes, have the potential to make cancer treatments less invasive.

They were created in 2011 by a team led by Gang Zheng, associate research director of the Princess Margaret Cancer Centre, University Health Network and professor of medical biophysics at the University of Toronto’s Temerty Faculty of Medicine.

“Porphysomes are a first-in-class lipid nanoparticle to have intrinsic multifunctionality covering multiple cancer types and different clinical applications,” says Zheng.

His team created porphysomes after failed attempts to load large amounts of porphyrin, an algae-derived pigment with therapeutic potential, into conventional lipid nanoparticles. Led by graduate student Michael Valic, the researchers spent the next decade embarking on a journey to translate their serendipitous discovery from bench to bedside.

The team found porphysomes had the ability to naturally accumulate in tumours but not in healthy tissues, and could absorb light for imaging and light-based therapies. The nanoparticles could also be used to deliver drugs to tumours and to bind radioisotopes for PET imaging or radiotherapy.

Remarkably, the researchers saw the same results in multiple cancer types – including colon, lung, oral, ovarian, pancreatic and prostate – and across a wide span of preclinical models.

Now, Zheng and a team of clinical researchers at UHN will assess the safety of the porphysomes in 15 patients with advanced ovarian cancer, in a world-first clinical trial.

The trial team is co-led by Stéphanie Lheureux, a clinician investigator at Princess Margaret Cancer Centre and an associate professor of medicine at the Temerty Faculty of Medicine, and Amit Oza, head of the division of medical oncology and hematology at Princess Margaret and professor of medicine at Temerty

The porphysomes will be labelled with a radioactive form of copper called Cu-64, allowing the researchers to track where the nanoparticles go and how quickly they break down.

The phase 1A trial is a big step forward in bringing this made-in-Toronto innovation out of the lab and into the clinic – but getting here wasn’t easy.

One of the biggest hurdles the research team faced was proving that they could produce clinical-grade Cu-64-labelled porphysomes that met the quality standards for human drugs.

To address this challenge, Zheng enlisted the help of Raymond Reilly, a professor in the Leslie Dan Faculty of Pharmacy and the director of the Centre for Pharmaceutical Oncology (CPO). As a trained nuclear pharmacist, Reilly’s expertise in making clinical quality radiopharmaceuticals – drugs that contain a radioactive isotope – was instrumental in helping the researchers scale up from preclinical to clinical studies.

Reilly also oversees the CPO’s Good Manufacturing Practices (GMP) facility, a production site where radiopharmaceuticals are made to strict quality standards for human use.

“This facility has allowed us to support a lot of different collaborative and translational research opportunities because we provide the necessary bridge step to move from preclinical to human studies,” says Reilly.

To secure Health Canada approval for the trial, Reilly and his team made several batches of Cu-64-labelled porphysomes that passed multiple quality assurance tests.

He notes that because of the short half-life of Cu-64, each dose of the drug must be custom made when a patient is enrolled. The radioactive copper is made and shipped from the University of Wisconsin–Madison to the GMP facility, where it is attached to porphysomes. Reilly’s team tests each batch before it is delivered to the clinical trial team at Princess Margaret.

Zheng says Reilly’s role in developing the protocol was “critical” in Health Canada’s decision to approve the trial.

“Without Professor Reilly and the GMP facility, the journey to bring this discovery to patients would have been even longer,” Zheng says.

Positive results from this trial, which Zheng hopes will be complete within the next year, would pave the way for a phase 1B trial to assess the safety of porphysomes in patients with different cancer types.

“I believe the biggest potential for porphysomes is in minimally invasive treatments for early-stage cancers like early-stage lung cancer,” says Zheng.

Back in the lab, he and his team are working to understand why porphysomes accumulate in tumours and how they generate an immune response beyond the cancer site.

For Reilly, the successful launch of this clinical trial is a testament to the power of collaboration in taking innovations from the lab into the clinic.

“Porphysomes are a homegrown technology discovered here in Toronto, and it needed a homegrown solution to take it to the next stage. It was the perfect opportunity to link the expertise and resources we have at U of T to advance a new cancer nanomedicine that could potentially impact patients around the world.”

This work was funded by the Ontario Institute for Cancer Research, Princess Margaret Cancer Foundation and Terry Fox Foundation. The GMP facility was supported by funding from the Canada Foundation for Innovation, Ontario Research Fund and the Leslie Dan Faculty of Pharmacy.