Industry that takes advantage of pioneering research. For a cutting-edge technology, cell therapy has a surprisingly long history. Indeed, the idea of injecting living cells into a patient originated in the nineteenth century.
Although scientists’ early rudimentary attempts did not really work, subsequent research proved more fruitful and today the technology has led to massive investment from research institutions and companies seeking to grow the cells needed for the procedures.
There are two categories of cell therapy, which is also known as cellular therapy or cytotherapy. One is used in mainstream medicine when a human cell is transplanted from a donor into a patient and, although such research has can be controversial when it involves human embryonic material, by and large the feeling is that it holds great promise.
The second category is more controversial and is practiced in alternative medicine where it continues the practice of injecting animal materials in an attempt to cure disease. However, the practice is beset by claims that it is not backed by medical evidence.
The origins of cell therapy can be traced to Charles-Édouard Brown-Séquard (1817–1894) who unsuccessfully injected animal testicle extracts in an attempt to stop the effects of aging.
His work was followed in 1931 by Paul Niehans, who attempted to cure a patient by injecting material from calf embryos. Niehans claimed to have treated many people for cancer with the technique, although his claims have never been fully validated by research.
In 1953, more credible breakthroughs were made with researchers discovering through tests on laboratory animals that rejection of transplanted organs could be prevented by pre-inoculating them with cells from donor animals, followed in 1968, in Minnesota, USA, by the first successful human bone marrow transplant.
Today, the procedure has been extended to other kinds of therapy such as treating damaged knee cartilage and the use of stem cells.
T cells have shown themselves capable of fighting cancer cells as part of immunotherapy treatment and research is offering hope to victims of neurodegenerative diseases, heart disease and diabetes.
All of this activity places pressure on the cell therapy manufacturing industry with a major problem being the move towards personalised treatments which require smaller runs of product rather than a mass produced off-the-shelf one.
One of the breakthroughs came when scientists at The University of Nottingham developed a new substance which could simplify the manufacture of cell therapy.
There are two phases in the production of stem cell products; proliferation (making enough cells to form large tissue) and differentiation (turning the basic stem cells into functional cells).
The environments required for the two phases are different and, up until the team’s breakthrough, a single substance that does both jobs had not been available.
However, the researchers have created a new stem cell micro-environment which allows both the self-renewal of cells and their evolution into cardiomyocyte (heart) cells.
The hydrogel they devised contains two polymers and creates an alginate-rich environment which includes a chemical switch which makes the environment collagen-rich when the cell population is large enough, a change that triggers the next stage of cell growth.
Nottingham University Professor of Advanced Drug Delivery and Tissue Engineering, Kevin Shakesheff, said: “The discovery has important implications for the future of manufacturing in regenerative medicine.
“This field of healthcare is a major priority for the UK and we are seeing increasing investment in future manufacturing processes to ensure we are ready to deliver real treatments to patients when products and treatments go to trial and become standard.”
Also part of the team was Glen Kirkham, a post-doctoral researcher in stem cells at the university, who believes that much remains to be achieved in the field.
He said: “Assessing where we are with stem cell therapy depends on which aspect you examine.
“If you take bone marrow transplants, that has been successful and is well developed, but people don’t always associate it with cell therapy. Other applications such as the use of stem cells are not yet as well advanced.
“What drives our work at Nottingham is the needs of medicine and the thing the manufacturers said would assist them was a product that could make it easier to produce cell therapies.
“Medicine is going is towards personalised treatments rather than off-the-shelf products so we set out to develop something that would make it more cost- effective to make something personalised rather than mass produced.
“Manufacturers are looking for technologies that are economically viable and since we made the announcement, work has continued to develop the idea.
“Although we concentrated on heart cells, we are also looking to expand it into a variety of applications. It’s about new ways of thinking and pushing the boundaries.”
Manufacturers can also see the potential and a lot of investment has gone into a sector which has attracted some significant players.
For instance, this year alone has seen a number of major announcements, including from Lonza, a global leader in cell therapy manufacturing, and biopharmaceutical company TiGenix who signed an agreement for the supply of TiGenix’s eASC product, Cx601, which is being developed for the treatment of Crohn’s Disease ,with much of the work happening in Walkersville, Maryland, US.
Other developments have included an announcement from WuXi PharmaTech (Cayman) Inc, which operates in China and the United States, that it will begin construction of a new, 145,000-square-foot cGMP facility in Philadelphia for the manufacture of cell therapy products.
The plant will concentrate on viral vectors such as chimeric antigen receptor T cell (CAR T cell) therapies, cells harvested from a patient’s body, engineered to target specific cancers then reintroduced into the body.
The complex will be WuXi’s third cell therapy manufacturing facility when it becomes operational in mid-2016 and Dr Ge Li, Chairman and CEO of WuXi PharmaTech, said: “Cell therapies like CAR T cells offer important new treatment options for cancer patients.”
In addition, US biopharmaceutical firm NeoStem, Inc. announced the expansion of manufacturing services under an agreement between its wholly-owned subsidiary PCT, and Kite Pharma, Inc.
For Dr Robert A. Preti, Chief Scientific Officer of NeoStem and President of PCT, such investments will support new thinking in the cell therapy manufacturing industry.
He said: “The expansion of NeoStem’s arrangement with Kite allows us to continue providing innovative, reliable and high quality manufacturing expertise to cell therapy developers who are researching potentially life-changing treatments for patients across many therapeutic areas.”
“The discovery has important implications for the future of manufacturing in regenerative medicine. This field of healthcare is a major priority for the UK and we are seeing increasing investment in future manufacturing processes to ensure we are ready to deliver real treatments to patients when products and treatments go to trial and become standard.” – Kevin Shakesheff, Nottingham University Professor of Advanced Drug Delivery and Tissue Engineering