Recently, a study conducted by the research team from the Imperial College London published in the Cancer Cell showed that supercharged natural killer (NK) cells capable of mass production can effectively fight cancer. This personalized treatment involves reprogramming of immune cells, marking the next generation of cutting-edge immunotherapy following CAR-T therapy.
In this study funded by the charity Bloodwise, the researchers created a genetically engineered cell called CAR19-iNKT, which simultaneously targeting CD19 and CD1d, protecting patients from aGVHD (acute graft-versus-host disease) through its iTCR integrity. And αGalCer and ATRA can enhance the reactivity of CAR19-iNKT cells.
It is well known that current CAR-T cell therapies are expensively tailored to each cancer patient, costing about £300,000 per patient. But the scientists agree that their new CAR-T therapy can solve this thorny problem, can be mass-produced and no longer subject to individual restrictions, in which a batch of products can be used for multiple patients at the same time, hopefully reducing treatment costs tenfold.
New research shows that CAR19-iNKT eliminates all cancer cells in 60% of mice, and 90% of mice experience long-term survival. Currently, researchers are considering human trials.
CAR-T Cell Therapy
Professor Anastasios Karadimitris, senior author of the paper, said: “Early research shows that this well-designed supercharged immune cell in the laboratory is expected to become a new treatment option for cancer patients.
Among them, as a new type of immunotherapy, CAR-T involves extracting immune cells from the blood of a patient and engineering it in the laboratory to obtain accurate recognition and destruction the supercharged immune cells of cancer cells. Then, the engineered new anti-cancer cells are multiplied in the laboratory, and finally, the anti-cancer army is smoothly returned to the patient to play a role.
Currently, this approach has been approved for the treatment of leukemias and lymphomas, and contributes to up to one-third of patients without other treatment options entering the long-term complete remission period. In this regard, Professor Karadimitris of the Imperial College of Hematology at the London Imperial College explained that this means that we can provide patients with a promising treatment, not just talking about hospice care with patients.
CAR19-iNKT Cell Therapy
The general CAR therapy is based on T cell reprogramming. However, in this study, scientists at Imperial College London used a different type of immune cell, called iNKT.
Although these cells are very rare in vivo, the researchers found that CAR19-iNKT is more effective at eliminating cancer cells than CAR-T cells. In the mouse lymphoma model, 90% of mice treated with CAR19-iNKT cells achieved long-term survival, while mice treated with CAR-T achieved a survival rate of only 60%.
And simultaneously targeting CD19 and CD1d may induce a deeper anti-tumor response, limit immune escape associated with loss of CAR target, and ultimately reduce disease recurrence. The mice with the highest tumor burden in the early stage subsequently relapsed after receiving immunotherapy. After receiving CAR19-iNKT treatment, a second remission was observed in four of the mice, further highlighting the importance of early deep remission.
In addition, the researchers were surprised to find that CAR19-iNKT cells were able to reach the brain and also cope with large tumors. This means that one day the technology is used to treat brain tumors as well as other cancers such as prostate and ovarian cancer.
An Expected Choice for Fighting Cancer
Dr. Alasdair Rankin, Bloodwise’s Director of Hematology Research, said: “The CAR-T drug introduced by the NHS is currently effective for a large number of patients, but not everyone, and the cost of treatment is quite expensive.”
“Although, by comparison, CAR19-iNKT is still in its early stages, it depicts the future of this treatment, expected to become a cheap and mass-produced therapy with highly effective anti-tumor activity. If successful, it will bring life-saving treatments to more patients.”
Dr. Antonia Rotolo, the first author of the study, explained: “Currently, the production of CAR-T cells requires the use of patients’ own T cells. But iNKT cells can come from healthy individuals and do not need to be matched to patients which is different from T cells. This means that CAR19-iNKT cell therapy can achieve spot treatment, i.e. off the shelf.
In addition, she added that next this technology will be tested on patients. Although the team has demonstrated in animal experiments that this method can eliminate cancer cells, it cannot predict potential side effects. Therefore, the researchers will study this through patient trials.
Currently, Imperial Innovations, a technology commercialization partner of Imperial College London, has applied for patents for basic cell processing technology and has worked with Professor Karadimitris on commercial applications.