Cancer is a huge problem that afflicts humans. With the development of medical technology, the survival rate of cancer has been greatly improved after the emergence of treatment methods such as chemotherapy and radiotherapy, but the life of a large number of cancer patients still cannot be saved. Therefore, Biotherapy has emerged in this era and has played a pivotal role in cancer treatment in the recent time.

Matter-of-factly, there are various biological treatment modes, for example, immunotherapy, gene therapy, etc. Meanwhile, cancer immunotherapy can be broadly subdivided into non-antigen-specific and antigen-specific categories. The former deals mainly with nonspecific immune stimulation and immune checkpoint inhibitors, whereas the latter focuses on cancer-specific T cells and various therapeutic vaccination approaches. Car-T therapy, as a kind of cancer immunotherapy, is favored by research institutions and pharmaceutical companies in the field of cell therapy.

This article mainly introduces the Cart T technology and its clinical application, and widely discusses the Car-T immunotherapy in the cell field.

What is Cart T?
Let’s start with the basics:what is Cart T Cells and Car-T technology?
You may have known about T-lymphocytes during the learning process of high school biology, which is a kind of pluripotent stem cells derived from bone marrow. For tumors, the main killer of our own immune system is T cells. If we compare the billions of cells in our body to the billions of people in our country, the T cells are like the troop that guards the country, garrisoning in our bodies and getting ready for the war against tumor cells. The researchers used genetic engineering technology to bind Car, a chimeric receptor capable of specifically recognizing and binding to a tumor antigen, with the activation motif T cells to express specific Cars, thereby having the ability to specifically recognize and kill tumor cells. Car T cells have attracted attention from the society due to its unique ability and its advantages of high killing and affinity.

Car-T technology, in brief, is to transform the functional genes that recognize specific targets of tumor cells into T lymphocytes of patients through genetic engineering methods, so that T cells can recognize tumors and become tumor-specific T cells for tumor treatment.

Clinical Application of Car T
As a cellular immunotherapy, Car T has the unparalleled advantages of traditional treatment methods (such as radiotherapy and chemotherapy). Car T treatment can specifically kill tumor cells on the basis of reducing damage to normal cells, moreover, there are no toxic and side effects of radiotherapy and chemotherapy, which can greatly relieve the pain of cancer patients. At the same time, this therapy has a comprehensive anti-cancer effect and is effective in the treatment of metastatic or multiple malignancies, and is equally effective in patients who have relapsed after treatment. In addition, the reconstitution of Car T cells can enhance the body's immune function and can fight tumors for a long time. Car T treatment has entered clinical trials for more than 18 years, which mainly involved solid tumors and hematologic tumors. The most successful clinical application of Car T cell technology is the treatment of hematological malignancies, which may be related to factors such as strong specificity of tumor-associated antigens and weak immunosuppressive effects of the tumor microenvironment.

Nature Medicine released a report about the use of Car T cells in the treatment of 11 cases of children who suffered from neurofibroma in 2008, including 6 cases improved. This is the first clinical application of Car T cell technology.

At the 55th Annual Meeting of the American College of Hematology at the end of 2013, CAR-T cell therapy received special attention. The Sloan Kettering Cancer Center, the University of Pennsylvania Cancer Center, and the National Cancer Institute’s three research groups reported on early anti-CD19 CAR-T cells clinical trials in both children and adults’ B-cell malignancies (including chronic, acute lymphoblastic leukemia and B-cell lymphoma). According to their report, although some patients have undergone multiple chemotherapy and have already developed relapse or resistance, the effective rate of CAR-T cell therapy response can still reach 60% to 80%.

However, Car T cell therapy still has non-negligible side effects. Although, due to the limited number of cases, the researchers could not come to a systematic conclusion, it has the side effects of various clinically common tumor treatments, more crucially, it is prone to the phenomenon of attacking normal cells due to recognition errors, which is called "off-target effect". At present, the greatest side effect of CAR-T cell therapy is the cytokine release syndrome. The injected T cells release a large number of cytokines, which may lead to dangerously high fever and drastic blood pressure drop. Some patients may need to take additional measures.

Can CAR-T immunotherapy completely overcome cancer?
First of all, it needs to be emphasized that the tumor is a heterogeneous disease, which means that even if all patients suffer from leukemia, the cause and treatment of different people are different. Therefore, there is a huge gap between the unique case of recovery and the complete resolution of cancer.

Secondly, from the current data, the short-term data of Car-T immunotherapy is good, but patients will soon relapse. Juno's JCAR015 Phase I clinical data showed that the complete remission rate in patients with acute lymphoblastic leukemia was 87%, which means that 87% of patients could not find cancer cells after treatment. However, about 60% of these 87% of patients will soon relapse, and only 59% of those who live over 6 months. Thus, even in the leukemia area where CAR-T is best at present, it is currently unable to "conquer" it.

Furthermore, most of the current CAR-T targets the CD19 antigen, and CD19 is only expressed on B lymphocytes, so it can kill B lymphocyte-derived acute lymphoblastic leukemia and non-Hodgkin's lymphoma, but for other tumors is completely powerless. Of course, many companies have begun to try to make CAR-T recognize antigens of solid tumors (such as liver cancer and kidney cancer). However, on the one hand, there are few such antigens. On the other hand, the microenvironment of many solid tumors is complex, which cannot play a role in immunity system, so at present there is no CAR-T that can work on solid tumors. In other words, CAR-T can only treat some hematological tumors at present, and the incidence of these blood tumors is relatively low.

Overall, although Car-T immunotherapy has side effects and various shortcomings, its emergence has indeed given us great hope. Researchers predict that the hope of future cancer treatment must be based on the combination therapy with immunotherapy being involved.

Author's Bio: 

As a leading chemical supplier, BOC Sciences keeps close watch on the recent research interests in the pharmaceutical industry and is increasingly involved with cancer therapy. To accelerate the drug discovery and design process, BOC Sciences offers a comprehensive collection of small molecule inhibitors for selection and a wide range of services, such as Carbohydrate synthesis, Bioconjugation, Biosynthesis, Formulation Service, Virtual Screening, etc.