What is CAR-T Therapy?
Chimeric antigen receptor T cells (also known as CAR T cells) are T cells that have been genetically engineered to produce an artificial T-cell receptor for use in immunotherapy.
CAR-T cell therapy uses T cells engineered with CARs (usually scFv or sdAb) for cancer therapy. The premise of CAR-T immunotherapy is to modify T cells to recognize cancer cells in order to more effectively target and destroy them.
Affinity of the extracellular binding domain to antigen significantly affects the targeting and killing ability of CAR-T cell.
A.J. Smith et al. 2016. Chimeric antigen receptor (CAR) T cell therapy for malignant cancers: Summary and perspective
Workflow of Common CAR-T Therapy Development
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- The evaluation standard of a therapeutic antibody is first its biological function and then affinity etc..
- So functional assays are conducted right after the primary screening
- The screening scale is larger to increase the chance of getting leads with good function.
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- ScFv, but not mAb, is expressed in CAR lead generation.
- Because the role of an antibody in a CAR-T development is mainly a targeting tool, affinity is the top consideration when selecting scFv or sdAb candidates.
- Specificity test can be performed according to customer requirements.
- The function of CAR-T cells not the scFv or sdAb itself should be validated in a CAR-T development project.
Service Highlights
Antibody discovery strategy specially designed for CAR lead generation
- Adopting affinity ranking by SPR in lead generation stage to ensure the delivery of high affinity leads
- Well-established antibody optimization platforms for scFv and sdAb
- Multiple in vitro bioassays are provided to validated CAR-T cell function
Capability of generating both scFv and sdAb, each modality with 2 technical solutions
- Hybridoma/single B cell screening/sdAb naïve and immunized library
Successfully deliver over 20 lead generation projects to CAR-T therapy companies
Downstream services are available, including plasmid and lentiviral vector process development and GMP manufacturing
CAR Expression
Figure 1. Representative of flow cytometry analysis of anti-CD19 CAR-T cells and non-transduced control cells 10 days after transduction. Cells were stained with anti-CD3 antibody and anti-FLAG (CD19-FLAG) antibody.
Functional Validation
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Figure 2. Functional validations of anti-CD19 CAR-T cells. (A) Cytotoxicity assay was performed to validate anti-CD19 CAR-T cytotoxic function at a ratio of 20:1 (CAR-T: Raji) for 24 hours. Raji (CD19 positive) cells were engineered to express luciferase and the cytotoxicity effects can be inferred by the reduction of bioluminescence signal. (B) Cytokine production by activated CD19 CAR-T cells in response to its target - Raji cells. The supernatant was analyzed by ELISA for IFN-γ secretion from anti-CD19 CAR-T cells.