The Complete Guide to Global Clinical Trials of CAR-T cell therapy

CAR T immunotherapy(chimeric antigen receptor T cell immunotherapy) is one of the most potential technologies in the field of cancer therapy. Compared with other tumor treatment methods, such as surgical resection, radiotherapy and chemotherapy, small molecule targeting drugs, monoclonal antibody drugs, and hematopoietic stem cell transplantation, CAR-T cell immunotherapy is more advantageous with higher precision and flexibility.

Currently, two CAR-T cell immunotherapy products have been approved worldwide, namely Novartis KymriahTM and Kite Pharma's Yescarta.

The number of global clinical trials of CAR-T therapy is increasing dramatically. According to the Cancer Research Institute (CRI), as of February 2018, a total of 404 CAR-T projects worldwide are in clinical trials, mainly headed by the United States and China. Among them, there are 171 in the United States in clinical trials, and 152 in China, accounting for 79.95% of the global CAR-T cell therapy and becoming the world's two giants of CAR-T cell immunotherapy.

At present, the CAR-T project in clinical research involves more than 47 targets. From the distribution of target sites, clinical trials of CAR-T cell therapy mainly focus on Cd19, CD20, CD22, GPC3, BCMA and other popular targets. From the distribution of CAR-T therapy targets in the United States, CD19-targeted clinical trials accounted for more than 40%. Previously, two CAR-T products approved by Novartis and Kite Pharma were also targeted at CD19. Similar to the distribution of target sites in the United States, the number of CAR-T clinical trials targeting CD19 in China is also over 40%.

The target determines the direction of the indication. In terms of indications, CAR-T cell immunotherapy has been proven to have made breakthroughs in the treatment of hematological malignancies, showing good targeting ability, lethality and persistence. The two CAR-T products approved by Novartis and Kite Pharma are also suitable for suitable for acute lymphoblastic leukemia and B-cell lymphoma, respectively, and are still expanding to other hematological tumors, such as follicular lymphoma, cell tumors, multiple myeloma, etc.

CAR-T is currently making relatively slow progress in solid tumor applications. It is reported that about 75% of the CAR-T clinical trials in the world are mainly used for blood tumors such as leukemia and lymphoma. Only a small part of the CAR-T project is for solid tumors such as liver cancer and lung cancer. On the one hand, there are large differences in the traits of solid tumors and blood tumors. Highly heterogeneity makes CAR-T therapy more difficult to treat solid tumors and the target selection is also one of the major challenges faced by CAR-T therapy. On the other hand, solid tumor-associated tumor antigens are not only expressed in tumor tissues, but also in normal tissues. The antigen even maintains the normal physiological function of the tissue. The improvement of the recognition specificity of CAR-T cells, and the reduction of the possibility of CAR-T cells attacking normal tissues becomes another major challenge for CAR-T to treat solid tumors. In addition, the homing and activation maintenance of CAR-T cells in solid tumors is also one of the challenges.

The side effect of CAR T cell therapy is also a challenging difficulty to get over. CRS is one of the common adverse reactions to CART cell therapy. CRS is a non-antigen-specific toxicity caused by high-level immune activation and is associated with increased levels of circulating cytokines including IL-6 and IFN-?. The mechanism is that the T and B lymphocytes, NK/T cells and macrophages, etc. release a large number of cytokines and chemokines after intravenous infusion of CART, and the inflammatory reaction caused by these inflammatory mediators causes tissue damage, resulting in Microvascular disease, heart failure, and even death. The clinical manifestations are nausea and vomiting, headache, dizziness, rapid heart rate, blood pressure drop, rash, chest tightness, shortness of breath and so on.

In the future, with the discovery of more targets and the mechanism of action, as well as the development of relevant clinical trials, the application of CAR-T in solid tumors has broader development prospects.

Author bio

As a global company, Creative Biolabs has more than 200 talented and well-trained scientists located in different continents working closely with partners from the entire world to develop and produce medicines of tomorrow. Specifically, we are the established leading expert in TCR and CAR T&NK cell immune therapy development, as we offer the one-stop custom services that cover the entire new drug development pipeline. Additionally, we also offer an exclusive line of ready-to-use TCR and CAR T&NK cell construction products, such as virus packaging, purification, expansion and titer determination kits. Furthermore, we have built up a unique unparalleled CAR construction and production platform for all four CAR generations.

Creative Biolabs was founded by scientists who are dedicated to conquering cancer, optimizing the drug development process, leveraging accessible resources.