CAR Design and Construction

The CAR is the most essential element of CAR-T therapy; therefore, the development of CAR-T cell therapy relies heavily on how to acquire CARs that specifically target cancer antigens. Protheragen offers various services and platforms such as end-to-end CAR molecule designing, construction, validation, CAR-T cell preparation, and characterization that assist with the various stages of CAR-T therapy development.

Overview of Chimeric Antigen Receptors

Chimeric antigen receptors (CARs) are artificially designed proteins, the central role that each structural element within the CAR molecule plays in controlling T cell function. It is handily ascertained that numerous strategies focus on further improving the CAR design or combining its activity with other regulatory circuits to control functional aspects more precisely. There are non-viral methods like transfection and viral methods that employ vectors such as retrovirus or lentivirus, that can be utilized to transfer CAR genes into T cells.

Fig.1 Schematic of CAR designs. (Heard, A., et al., 2021)

Structure of Chimeric Antigen Receptors

CAR structures include the extracellular antigen recognition site, hinge, transmembrane region, and one or multiple intracellular signaling. The external recognition portion typically consists of scFv or antigen-binding domain that is specific for certain antigens on targeted cancer cell's surfaces, this external recognition portion can be genetically engineered to guarantee that antigen is attached efficiently. A vigorous signaling cascade that promotes CAR-T cell target antigen-specific activation and proliferation is set off by the internal signaling region after the engagement of CAR with the selected target antigen.

Table 1 Typical components employed in the design of CAR molecules

Our Services

As leaders in the development of CAR-T therapy, our goal in CAR designing services is to develop effective and precise therapeutics for a variety of conditions. Employing advanced design strategies and the application of technology platforms, we ensure the optimization of each component of the CAR. CAR development services include established and innovative types of CARs that are customized for specific therapeutic objectives and aim at ensuring CAR-T therapy safety and efficacy by prioritizing humanization and low immunogenicity.

CAR Components Design Services

• Design and Screening of scFv: Develop scFvs that are capable of binding to a target antigen with high affinity and specificity and possess functional antigen binding activity.
• Optimization of Linkers: Design and create linkers with different lengths to add more flexibility between VH and VL, this will influence the binding affinities.
• Optimization of Hinge Regions: Construct hinges of different lengths for enhanced spatial flexibility and offer diverse transmembrane domains to improve CAR surface expression and functionality.
• Selection of Co-stimulatory Molecule Structures: The integration of various generations of co-stimulatory domains enables us to adjust the safety, duration, and strength of T cell activation.

Novel CAR Development Services

• Ligand-based CARs
• Peptide-based CARs
• Dual Antigen Targeting CARs

• Trivalent CARs
• Gated CARs
• Armored CARs

Leveraging the EndureCART^TM technology platform, bioinformatics, and molecular biology skills, we assist specialists with the process of CAR-T therapy development right from its conception to validation. It does not matter if you're interested in CAR applications in hematologic malignancies, solid tumors, or other diseases, we strive to provide the very best solutions, tools, and insights for your work. If you are interested in our services and platform, simply get in touch with us.

For research use only, not for clinical use.