Chimeric Antigen Receptor Technology

Surfarray™ Cell Microarray Technology Search the Best-in-class CAR-T Cells for Immunotherapy www.creative-biolabs.com/car-t/ With unrivaled expertise and experience in the discovery and development of various immunotherapies, Creative Biolabs independently developed a novel Surfarray™ Cell Microarray Technology to support our clients' cellular therapy research. We offer Surfarray™ Cell Microarray Technology to best suit your program requirements. Background In medical research and drug discovery, it is often highly advantageous or even essential to identify the cell surface proteins that are targeted by a molecule of interest. Cell microarray technology is a powerful tool for the discovery of human cell surface and secretory protein targets for various antibodies, proteins, and small molecules. This method can process thousands of units simultaneously, enabling a wide screening on only a few slides, which could increase the output significantly. By doing so, a global map of cellular functions can be generated to further our understanding of both normal biological and disease processes. Creative Biolabs' unique and highly sensitive Surfarray™ cell microarray technology allows us to provide fast, accurate, and efficient solutions to our customers around the world: • Discover novel, high quality, and developable cell therapy targets. • Detect specific interactions with a high degree of sensitivity. • Widely covering known plasma membranes and secreted protein subclasses. • Explore safety liability of lead candidates.

Key Applications of Cell Microarray Technology Cell-based microarrays can be used in various applications. Our case studies focus on providing more details on receptor identification, targeted deconvolution, and specific screening of biotherapeutics such as CAR-T cells and antibodies. Our key applications include but are not limited to the followings: Target Deconvolution Target deconvolution has traditionally been a well-recognized bottleneck in phenotypic discovery. Cellular microarray technology is well suited for target deconvolution. It ranges from the primary targets of revealing antibodies or small molecule compounds identified by phenotypic screening to commercially available drugs. Our microarray technology is widely used for CAR-T and antibody target deconvolution: • Discover novel, high-quality, and developable cell therapy targets. • Receptor molecules are targeted by phenotypic molecules. (antibodies, scFvs, Fc-fusion proteins, etc.). • Identification of disease-specific antigens by screening patient sera. Receptor Identification Our cell microarrays are optimized for the identification of physiologically relevant cell surface interactions, which can vastly increase the chances of finding a ligand's receptor. It recognizes cell surface receptors and secreted targets of a wide range of molecules ranging from purified proteins to more complex ligands such as whole cells: • Natural soluble proteins and peptides • Live viruses and virus-like particles (VLPs)

• Cell surface derived ligands • Whole cells expressing the ligand of interest Off-target Profiling Toxicity derived from off-target binding to either cell surface or secreted proteins causes serious concern in drug development. Our off-target analysis is used to assess off-targets of plasma membranes and secreted proteins expressed in human cells. Highlights: • Has a very low false positive/negative number. • Can predict/interpret reduced bioavailability due to off-target binding. • Can inform pre-clinical toxicity model selection and reduce animal testing. Off-target profiling • Monoclonal or bispecific antibodies • ScFvs, Fabs, or antibody derivatives • Peptides • Protein ligands • Labelled small molecules CAR-T Cells Specificity Screening To ensure patient's safety, the risk of triggering an inappropriate immune response should be minimized, such as unanticipated off-target binding of the engineered CAR-T cells. Our cell microarray technology can label and screen entire CAR-T cells and can be used to evaluate final engineered cells as well as precursor antibodies/scFv. There are two methods for targeted screening of CAR-T cells: • Screening of antigen recognition elements—scFv • Screening of engineered CAR T cells Early specific screening can help with the selection of the right scFv to maximize the chances of producing the most promising potential CAR T therapy. A more relevant off-target assessment can then be provided by screening the entire engineered T cells (or final scFv).

Novel Immune Checkpoints Discovery Identifying new immune checkpoint therapeutic targets provides important scientific value to our customers. Since many important immune checkpoint interactions have not been fully characterized, we use cell microarray technology to identify immunological checkpoint targets with high specificity. Contact us for case studies and we'll show you how to use cell microarray technology to identify immune checkpoint targets with high specificity. Creative Biolabs is dedicated to helping our worldwide customers shorten the time in the discovery and development of CAR-T cell therapy. We utilize proprietary drug design, study data, product candidates, advanced project life-cycle management, as well as real-time data to ensure the ideal outcomes. For more detailed information, please feel free to contact us. Creative Biolabs take the advantages of CAR-T strategy to help researchers accelerate the CAR therapeutic development and make history in fighting malicious cancers. References: 1. Freeth J, Soden J. SLAS Discovery. 2020 25 (2) 223-230. 2. Castel D, Pitaval A, et al. Drug Discovery Today. 2006 Jul 11;(13).. Email: [email protected]

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