CellRapeutics™ One Stop Solution for CAR-T/NK Construction

As a leading biotech service provider, Creative Biolabs is pleased to share its extensive experience acquired during the development of CAR-T technology. We provide one stop solution for generating CAR-T/NK and subsequent tests, from scFv discovery to clinical trials.

Chimeric antigen receptors (CARs), also known as chimeric T cell receptors, chimeric immunoreceptors or artificial T cell receptors, enable immune effector cells (usually T cells or NK cells) to recognize target cells with corresponding antigen and exercise their cytotoxic activity. The emergence and development of CAR-T technology makes complete cure of certain types of cancer achievable, which turns CAR-T into a superstar in the field of both biomedical research and clinical studies.

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Technically, a chimeric antigen receptor mainly consists of a single chain variable fragment (scFv) that recognizes antigens, an extracellular hinge with spacer element, a transmembrane domain and an internal signaling domain such as CD3ζ. With our cutting-edge technology and platform, Creative Biolabs can generate CAR-T efficiently while in a cost-effective manner. For example, we have multiple techniques to choose from in order to get the scFv fragment sequence, which is the most difficult and critical process.

CAR scFv Fragment Sequence Acquisition Platforms

Hybridoma Cell Line
Our Magic-Hybridoma™ Platform relies on the novel immunization adjuvant, Magic Mouse Adjuvant that enhances immune reaction with a trace amount of immunogen to generate enough antibody-producing B cells for hybridoma production. In addition, with the help of our Omni-Hybridoma Platform™ , hybridoma clones can be selected and expanded immediately after fusion, which eliminates the possibility of out-competition of valuable potentially slow-growing clones by its fast-growing or overgrowth counterparts.

Phage Display Library
Creative Biolabs has developed and commercialized a full range of integrated innovative services that are based on our extensive experience in phage display technology. With our powerful library collections, we can identify sequence information of scFv quickly and accurately.

DASS Antibody Sequencing
Database Assisted Shotgun Sequencing (DASS) can provide de novo sequencing service for purified monoclonal antibodies of all species with different isotypes and allotypes. This technology is very mature so that it can achieve close to 100% coverage and 100% accuracy. In this regard, we can take advantage of this powerful platform to sequence the variable region, or even the full length of heavy and light chain of a particular antibody.

CAR Construction and Four Generations of CAR Design
Next, we can ligate the scFv sequence into a lentiviral vector to generate a CAR construct for transduction. Depending on what elements this construct contains, it is classified as one of the following four generations.

First generation CAR contains the scFv and only one intracellular signaling domain, such as CD3ζ or FcεRIγ.
Second generation CAR consists of the scFv, and the co-stimulatory domain from CD28, which can enhance antigen-specific cytokine production and proliferation of CAR-T cells.
Third generation CAR is added with another co-stimulatory domain from 4-1BB (also known as CD137) on top of second generation. This domain increases persistence of CAR-T cells in vivo and thus enhances anti-cancer efficacy.
Fourth generation CAR has its functional domains controlled by small molecules, which limits the adverse effects of CAR-T cells such as “on-target, off-tumor” in vivo.

After successful construction of a lentiviral CAR expression plasmid, it is co-transfected with packaging vectors into 293T cells in order to produce enough viral particles. Later, these viral particles are used to transduce activated T/NK cells to generate CAR-T cells.

Finally, these fresh CAR-T/NK cells are evaluated for their designated functions.

In vitro CAR-T Function Test

CAR expression level Cytokine release performance
Killing efficiency
Proliferation rate

As additional service, Creative Biolabs offer in vivo analysis of CAR-T/NK cells in mouse, rat and non-human primate (NHP) animal to evaluate the anti-cancer effect and safety profile.

In vivo Analysis Animal Models

Mouse
Rat
Non-human primate (NHP)

With strong collaboration with many top medical institutes and hospitals around the world, Creative Biolabs also conduct clinical trials for customers who are developing new treatment for cancers using CAR-T/NK. We are by your side to push any promising immunotherapy forward for clinical application.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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