Biological therapy includes a variety of models, such as immunotherapy, gene therapy, regulation of angiogenesis therapy, small molecule targeting drugs and stem cells and tissue engineering regenerative medicine. Among them, cancer immunotherapy has received wide attention from academic institutions and pharmaceutical companies since it was selected as one of the most concerned major scientific fields by “Science” magazine from 2013. In the field of cancer therapy, CAR-T therapy has undoubtedly become a superstar of research institutions and pharmaceutical companies.

CAR-T refers to Chimeric Antigen Receptor T-Cell Immunotherapy. The principle is that T cells modified by chimeric antigen receptor can specifically identify tumor-associated antigen to improve the effects of T cells targeting activity, cytotoxicity, and persistence.

CAR-T refers to Chimeric Antigen Receptor T-Cell Immunotherapy
However, CAR T cell therapy can cause several alarming side effects, such as cytokine storms, encephalopathy, and B cell hypoplasia. The trickiest may be cytokine release syndrome. Patients with cytokines will have a fever, tachycardia, hypotension, capillaries, and respiratory. Patients with encephalopathy will become confused and convulsive while patients with B cell dysplasia will have repeated infections due to poor immunity in vivo. Therefore, bio-distribution study plays a significant role in tracking these molecules.

‘Biodistribution is a method of tracking where compounds of interest travel in an experimental animal or human subject. For example, in the development of new compounds for PET (positron emission tomography) scanning, a radioactive isotope is chemically joined with a peptide ( a subunit of a protein). This particular class of isotopes emits positrons (which are antimatter particles, equal in mass to the electron, but with a positive charge). When ejected from the nucleus, positrons encounter an electron and undergo annihilation which produces two gamma rays traveling in opposite directions. These gamma rays can be measured, and when compared to a standard, quantified.’

Based on CAR-T bio-distribution study, the proper delivery route and dosing regimen of CAR T cells can be elucidated clearly with the identification of durability. T cell migration and distribution to tumor tissues, which ultimately determine the final fate of these cells, are essential for anti-tumor effects. CAR-T bio-distribution study is also capable of analyzing T cell phenotype and tracking T cell response to re-challenge with tumor cells. At the same time, the tumor microenvironment contains multiple inhibitory factors to potentially suppress CAR-T cells. In order to prevent tumor cells from developing mechanisms to avoid the eradication by CAR-T cells, CAR-T biodistribution will help to analyze Tregs, Myeliod-derived suppressor cell (MDSCs), Immune checkpoint (PD-L1) and T cell suppressive cytokine. Taking advantage of CAR-T cell biodistribution study, multiple assays on the viability of CAR constructs can be performed to examine the efficacy of the next generation CAR.

As a new star in biological therapy area, CAR-T therapy has a rather bright future with its great potential. However, as a matter of fact, it is undeniable that the adverse effects of CAR T will bring many troubles to both patients and doctors, which indicates the importance of the CAR-T biodistribution study again. All in all, it is necessary for us to conduct CAR-T biodistribution study.

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