T cell therapy can extend the survival of cancer patients for several years
Release date: 2014-12-31
Pharmaceutical companies use immunotherapy to fight leukemias and lymphomas that are difficult to cure.
When immunologist Michel Sadelain first tested a genetically engineered anticancer T cell in 2007, he struggled to find patients willing to participate in the trial. His proposed treatment plan is to isolate some T cells from tumor patients and use genetic engineering techniques to improve them to have tumor recognition ability, and then inject T cells back into patients; mouse studies have shown that this treatment The method is feasible. But Sadelain did not vent their anger at their colleagues because they refused to provide patients. He said: "The treatment plan I proposed sounds like science fiction." "I have been thinking about this for 25 years. I still say to myself now, 'This idea is crazy.'"
Since then, Sadelain and other research teams have applied this “crazy idea†to patients with ineffective conventional therapies, and have obtained some early findings that show that this “crazy idea†can completely eliminate all leukemia symptoms in patients. This treatment is called adoptive T-cell transfer. Today, his research team at the Memorial Sloan Kettering Cancer Center in New York City is working to provide adoptive T cell metastasis to a wide range of patients who are required to participate in the trial.
Such genetically engineered modified T cells are commonly referred to as chimaeric antigen receptor (CAR) T cells. The American Society of Hematology (ASH) meeting was held in San Francisco, California from November 6th to 9th. Participants heard a lot of talks about the application prospects of CAR T cells in the treatment of leukemia and lymphoma. And poster display. Concerns have been raised about how safe the therapy is, how difficult it is to develop personalized T-cell therapies on a large scale, and how regulators will review this complex, unconventional treatment. These concerns have long plagued researchers in the field. However, studies have shown that patients with only a few months of survival survived the treatment of the therapy for several years; and some skeptics gradually eliminated concerns about the therapy after seeing the data.
Joseph Hedden, an analyst with Datamonitor Healthcare market research firm (based in London), points out that the number of patients (requiring this therapy) is quite alarming. Although the development of the therapy will cost a lot of money, it still tempts the pharmaceutical companies to make a clear decision to carry out research and development.
In the past three years, at least five large pharmaceutical companies have invested in the development of CAR-T cell therapies. There have been only a handful of medical academic centers supporting the field of T cell therapy research, and today, the pharmaceutical industry's great interest in T cell therapy dramatically reverses the stalemate in this field. Small biotech companies have sprung up and developed CAR T cells, including Kite Pharmaceuticals in Santa Monica, Calif., which raised 127.5 million when it went public in June. Dollar. This year, investors invested $310 million in another CAR-T cell therapy company, Juno Therapeutics, in Seattle, Washington. Hans Bishop, CEO of Juno Treatments, said: "There is no doubt that the direction of investment has changed."
Certain types of leukemias and lymphomas are caused by cancerous B cells that produce antibodies, while most of the development of T cell therapy is focused on developing treatments that kill this cancerous B cell. A protein called CD19 exists on the surface of most B cells. The researchers modified T cells to recognize CD19 proteins, and then used modified T cells to attack all CD19-expressing cells, thereby killing cancerous B cells (see " recruiting"). It is difficult to find proteins that are expressed only on the surface of tumor cells, and CD19 is a compromise: although CAR-T cell therapy sometimes removes all B cells (including cancerous B cells and healthy B cells), Patients can still survive in the absence of B cells.
Sadelain et al. reported at the ASH meeting that six lymphoma patients who participated in the same trial had disappeared after receiving treatment with the therapy. Carl June, an immunologist at the University of Pennsylvania in Philadelphia, said in another report that CD19-targeted therapy can reduce cancer in nine of the 23 patients with chronic lymphocytic leukaemia. burden. For the more serious cancer of acute lymphoblastic leukaemia, 27 patients have symptoms disappeared after treatment, and two years later they still have CAR T in their blood. cell.
However, some studies have highlighted that this therapy carries the risk of stimulating an immune response. Some patients died after receiving CAR-T cell therapy, and their death was associated with an abnormally high level of interleukin-6 in the body. Subsequently, at least five CAR-T cell trials were terminated in April. Interleukin-6 promotes the inflammatory response and increases the expression levels of other inflammatory molecules, and is a component of the body's normal response to infection. However, the strong immune attack by CAR T cells can cause the level of interleukin-6 to soar. The researchers adjusted the treatment plan to better monitor and manage the problem before they restarted the trial.
Citi is a New York City-based investment bank. Andrew Baum, director of the bank's global health care research unit in London, points out that these security risks and the difficulty of producing CAR T cells continue to discourage many pharmaceutical companies. He said that most multinational companies are sitting on the sidelines and are not involved in the development of CAR T cell therapy.
When CAR T cells enter the market, their prices will be very expensive. Baum noted that the price of bone marrow transplants exceeded $500,000, and some sponsors initially planned to make CAR T cell therapy more expensive than bone marrow transplants. He pointed out that the cost of CAR T cell therapy may be very high, forcing pharmaceutical companies to develop a special fee reimbursement program: only when patients benefit from CAR T cell therapy, they need to pay for the pharmaceutical company. Baum estimates that although the sales of CAR-T cell therapy will depend on a number of factors: for example, what competitive therapies will emerge, whether CAR-T cell therapy can be used to treat other tumors, but CAR-T cell therapy is at its peak Sales can still reach $10 billion a year.
For now, Sadelain, the technology founder of Juno Treatment, hopes that the pharmaceutical industry's focus on CAR-T cell therapy will promote this area of ​​development. He remembers that during the post-doctoral period, he tried his best to insert genes into T cells, and his colleagues asked him why he was so troublesome. He pointed out that this area has never had such an investment before. It's really unbelievable - sometimes he still licks himself to see if he is dreaming.
Source: LifeOmics
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