Empowered by leading technologies as well as years of experience in the field of CAR-T based cell therapy, Creative Biolabs has built all-round platforms to help worldwide clients with their cell therapy projects. With non-stop efforts, now, we are proud to present a new generation of CAR-T cells with a special switch for tumor immunotherapy.
Background of CAR-T Cells
The concept of chimeric antigen receptor T cell (CAR-T) was first proposed in 1989. In recent years, this new type of cell therapy is widely used and developed for tumor therapy. It has significant efficacy in the treatment of acute leukemia and non-Hodgkin's lymphoma and is considered to be one of the most promising treatments for cancer. Although two CAR-T cell-based therapies were approved by FDA, there are still some limitations need to be settled. One of them is how to control the degree of response of CAR-T cells and reduce the side effects caused by cytokine release syndrome (CRS). Fully understanding these needs, Creative Biolabs offers the switch CAR-T cell discovery service as an alternative solution.
Types of Switch CAR Constructions
For conventional CAR constructions, a single chain variable fragment (scFv) and co-stimulation domains are used for tumor antigen recognition and intracellular signaling, respectively. While, unlike traditional CAR, ACTR does not normally react with tumor cell antigens. ACTR requires adding an external antibody that specifically recognizes tumor cell antigens. The newly added antibody can not only recognize cancer cells but also activate T cells to perform tumor killer functions.
Fig 1. Synthetic receptor designs for targeting tumor antigens.
The tumor microenvironment is rich in inhibitory growth factors such as TGFβ and IL-10. Meanwhile, PD-L1 is expressed on the surface of tumor cells, which causes immunosuppression near the tumor. To get over these inhibition microenvironments, we are able to inhibit the PD-1 intracellular signals such as ITIM and ITSM. Using costimulation domains form CAR-T cells, the immunosuppressive microenvironments can be engineered from inhibition from activation.
Fig 2. Methods for engineering T cells resistant to immunosuppressive microenvironments.
A "suicide" switch such as icaspase 9 was introduced for CAR-T cell. Under normal conditions, the presence of icaspase 9 as a monomer does not affect CAR-T activity, but in the case of adding a small molecule such as rimiducid, icaspase9 can be dimerized, leading to apoptosis of T cells. This mechanism gives a hint to apply small molecules for the treatment of CRS. We offer the service to develop both "suicide" switch and "activate" switch. The intracellular space of the "activated" version of CAR-T cells are divided into two parts, which are in the "OFF" state. Under the action of small molecules, the two parts can be separated. With the increasing concentration of small molecules, the function of T cells to kill target cells is stronger. One of the appealing features of this type of CAR-T is tight control. It only has a killing effect when small external molecules appear.
Fig 3. Molecular strategies to control T cell activation.
Features of our Services
With the help of our well-established technologies and experienced scientists, Creative Biolabs is capable of offering CART-cell discovery service with a “switch”. We provide very flexible options for each specific case. Meanwhile, we are happy to make it accessible to all kinds of research and industrial customers. We are open to discussions, so please don’t hesitate to contact us for more information.
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