Well-suited antibody discovery strategy for CAR lead candidates
Chimeric Antigen Receptor T-cell Therapy (CAR-T cell therapy) harnesses genetically engineered T cells with CARs to combat cancer. CAR lead candidates primarily comprise the antigen-binding region and the signaling domain. The former is responsible for the specific recognition of cancer cells, while the latter triggers T-cell-mediated killing functions. Features like their small size and stability make scFv or sdAb the preferred choice for the antigen-binding domain in CARs, their affinity with antigen significantly impacts the CAR-T cells' ability to target and destroy cancer cells, while excessive affinity could potentially lead to CAR-T cell-related toxicity.
GenScript ProBio offers a comprehensive antibody discovery platform that is exceptionally well-suited for CAR lead discovery. What sets our CAR lead discovery platform apart is its diverse array of customized antibody discovery strategies, in-depth in vitro bioassays, and comprehensive in vivo pharmacology studies. Our goal is to assist you in identifying functionally validated CAR leads with the right affinity, while minimizing the risks associated with developability, immunogenicity, and thermostability.
Feel free to download the poster to discover how we create antibody leads for CAR-T therapy.
CAR-T cell therapy has several limitations, including CAR-T cell-associated toxicities, on-target/off-target effects, antigen escape, undesirable trafficking & tumor infiltration, and immunosuppressive microenvironment, etc..
CARs which serve as the targeting component, consist of an extracellular binding domain, a hinge domain, a transmembrane domain, and one or more intracellular domains, all of which influence the efficacy and safety of CAR-T cell therapy. When designing CAR molecules, various factors typically need to be taken into consideration.
GenScript ProBio created a comprehensive antibody discovery solution tailored for CARs, incorporating five distinct technical campaigns to yield diverse binders. Our offering sophisticated in vitro and in vivo bioassays, along with an industry-leading lead optimization platform. These tools swiftly identify CARs with robust specificity, suitable affinity, and impressive diversity, empowering you to capitalize on market opportunities quickly.
In Vitro Assay
In Vivo Assay
CAR lead candidates typically use sdAbs or scFvs as the ideal structural components, which need a suitable affinity for precise targeting while minimizing the risk of cellular toxicity. Furthermore, it's essential to consider the other attributes, such as antibody cross-reactivity, developability, stability, and candidate differentiation.
GenScript ProBio offers tailored antibody discovery solutions for CAR lead candidates, presenting five distinct technical campaigns for sdAbs and scFvs. Following initial screening, we will directly perform SPR affinity ranking to yield an array of binders with varied affinities. Through additional functional assays like epitope binning, cross-reactivity testing, and early developability testing, our services expedite the acquisition of high-quality CAR lead candidates with unique properties.
750+ projects completed
14 projects advanced to clinical trials
Extremely Fast, Minimal Diversity Loss
100+ projects completed
High capacity Exceeding 10^11, High diversity, High quality
1 FDA-approved drug ，6 global licensing deal; 150+ sdAb lead generation projects
GenScript ProBio has a comprehensive antibody engineering platform (antibody humanization, affinity maturation, developability optimization, Fc engineering) to optimize your antibody candidates:
ProBio's comprehensive CAR-T/NK in vitro pharmacology platform offers a range of services to support you in developing CAR cell therapy. Our services include the generation of CAR encoding vector, T cell activation and transduction, expansion of CAR-T cells, and functional assay for cytotoxicity and cytokine release.
CAR-T functional evaluation
The efficacy and safety of CAR-T need to be simultaneously verified in early pharmacology studies. Genscript ProBio provides a one-stop CAR-T in vivo pharmacology solution throughout the whole discovery process from drug design and screening to PCC confirmation, which will help you obtain high-potential CARs for optimal therapeutic outcomes.
Figure A：Solid Tumor（MDA-MB-231）,Single Dose CAR-T Treatment inhibit In Vivo Tumor Growth
Figure B：Single Dose CAR-T did not influence Mice Body Weight and Temperature (Data not show)
The quantities of circulating CART Cells
Figure C：Circulating CAR-T Cells in peripheral blood works as a three-phase kinetics diagram*
Figure D：CAR Positive T Cells can accumulate In tumor
Feel free to download the poster to discover how we leverage the naïve VHH phage display library and an integrated antibody engineering platform to create antibody leads for CAR-T therapy.
In this case study, an alpaca naïve VHH library was panned and screened by ROR1 proteins of 3 different ECDs and CHO-K1/ROR1 cell line to identify ROR1 VHH candidates. These VHH candidates were used to construct CAR-T cells and further evaluated by vitro functional assays, based on which final leads were selected for optimization by affinity maturation and ready for the development of CAR-T therapies.