Canada Joins the CAR T-Cell Club

With two highly publicized FDA approvals of breakthrough CAR-T therapies in as many months, a new era of cancer medicine is officially upon us. But how will the revolution be commercialized? That’s the multibillion-dollar question facing pharmaceutical industry engineers working to streamline the complex, expensive process of producing these lifesaving treatments.

Seeking a competitive edge in what could be a $20-billion industry by 2025, the government of Canada has teamed up with GE Lifesciences to build an innovation hub for the development of technologies and workflows for CAR-T and other cellular therapies. The new Center for Advanced Therapeutic Cell Technologies (CATCT) – part of the nation’s Centre for the Commercialization of Regenerative Medicine – opened for business in early October, smack in the middle of the FDA’s first two landmark CAR-T therapy approvals. Novartis was first to market in August with Kymriah, for children and adolescents with resistant or recurring forms of acute lymphoblastic leukemia. On October 18, a treatment developed by Kite Pharma (now part of Gilead Sciences) called Yescarta was approved for patients with certain forms of non-Hodgkin lymphoma and other large B-cell lymphomas.

Established with a CAD $20-million grant from Canada’s Federal Economic Development Agency for Southern Ontario (FedDev) matched by CAD $20 million in equipment and expertise from GE Lifesciences, CATCT is staffed by teams of scientists and bioengineers working with university and pharmaceutical industry partners to optimize and scale up the manufacture of adoptive cell technologies.

CELL THERAPY OVERVIEW

If you’re just tuning in to the cell-therapy phenomenon, you’re in good company. Although biotech insiders have been following the progress of these promising drugs for years, it has taken the first couple of approvals to put the public spotlight on what is being called the fourth new pillar of oncology – along with chemotherapy, radiation, and molecularly targeted therapies.

What makes these therapies so effective – and so different from any previous approach – is their use of a patient’s own immune system to seek and destroy disease-causing aberrations at the cellular level – permanently. Cell-based therapies are not pills or chemotherapeutics. Rather, they are the patient’s own immune cells, genetically re-engineered with disease-fighting properties specific to the patient’s condition.

CAR-T therapy is the most talked-about of several cell-based treatment approaches now under development. The acronym stands for chimeric antigen receptor, a special type of receptor that binds to a certain protein on the patient’s cancer cells. Genetic material from these CARs are added to disease-fighting T cells extracted from the patient’s blood and then grown under specialized laboratory conditions to create the millions of enhanced T cells required for therapeutic effect. The product is cryogenically preserved and returned to the treatment center for infusion back into the patient.

CAR-T therapies are designed as one-time “living” treatments that reprogram the patient’s immune system to thwart cancer’s recurrence for life. At least 20 CAR-T therapies are moving through clinical trials toward FDA review. Kymriah and Yescarta were both approved on a fast track after helping unprecedented numbers of patients achieve prolonged remission in clinical trials. The first two to be approved have several significant caveats – they’re appropriate for relatively small numbers of patients, can cause potentially lethal side effects, and cost hundreds of thousands of dollars to administer. However the potential benefits for patients with no other options are indisputable. Beyond cancer, cell-based therapies have enormous potential in the treatment of heart disease, neurodegenerative disorders, autoimmune diseases, and musculoskeletal conditions. Once CAR-T therapies evolves into front-line treatments, they could benefit an estimated 300,000 patients worldwide.

EQUIPPED FOR INNOVATION

The pace of progress in cell therapy research and clinical outcomes is largely outpacing industry expectations and, consequently, the available manufacturing technologies and systems. “It is increasingly clear that cell therapies and regenerative medicine will transform healthcare globally, but successful industrialization is now crucial to widespread adoption” said Kieran Murphy, CEO of GE Healthcare’s Life Sciences business. “This new center will enable us to work with cell therapy companies to push beyond existing technical limits.”

The new laboratory’s parent organization, CCRM, was established six years ago to capitalize on the existing academic, clinical and technology infrastructure already in place in Toronto – North America’s fourth largest metropolitan area. CCRM is the nexus of a 50-member consortium of corporate partners working to commercialize regenerative medicine.

 CCRM’s R&D team is staffed by more than 40 scientists and engineers with cell- and gene-therapy expertise spanning the basic research-to-manufacturing continuum. At the new center, teams of biologists, virologists and engineers from multiple backgrounds work on a fee-for-service basis with clients ranging from Big Pharma companies to university researchers to small start-ups to develop customized processing solutions. Customers retain all intellectual property and the rights to technologies, processes and assays developed through the collaboration.

GE’s Sefia is an automated multifunction system for purification, concentration, washing, and final formulation.

A state-of-the-art process development suite for cell and gene therapy workflows is equipped with two dozen 200-mL DASBox reactors and an ambr15 microscale bioreactor system for design-of-experiment development. The facility also features multiple rocking-motion and stirred-tank bioreactors in various configurations, providing the capability to operate at culture volumes up to 200 L. Cell processing and analytics equipment on-site include the GE’s Sefia automated multifunction system for purification, concentration, washing and final formulation and the GE Sepax II for automated cell washing and concentration. Other technologies include a range of in-line sensors, tangential flow and acoustic filtration systems, automated liquid handling and tissue culture robots, and an analytical suite featuring liquid chromatography-mass spectrometry and polychromatic flow cytometry.

“Developing advanced manufacturing solutions is right in our wheelhouse,” said Michael May, CCRM’s president and CEO. “With CCRM’s scientific and technological expertise, and GE’s deep knowledge of bioprocessing, plus the support of the Canadian government, this partnership was ideal for all parties, but the global regenerative medicine community will also reap the benefits.”