TCE Antibody Screening Applying Native-like KACTUS TCR-CD3 Complexes to Drug Discovery

KACTUS has leveraged its mature and high-efficiency recombinant protein expression platform to launch the brand-new CD3-TCR Complex Nanodisc and VLP series.

Advantages of our CD3-TCR Complex products features

• Full-length protein sequences
• Accurately replicate the native assembly of CD3 subunits and their physiological association with TCR.
• Ideal for diverse applications:

o   Animal immunization

o   Antibody screening

o   Epitope mapping

o   Structure-guided design

o   in vitro or in vivo validation

Experimental results confirm that KACTUS’s CD3-TCR complex Nanodisc and VLP products maintain dual biological binding activity, interacting effectively with both CD3 antibodies and their corresponding pMHC complexes. 

Significance of TCR-CD3 Complex in Antibody Discoveries

For antibody discovery, particularly in developing T-cell-activating therapies like TCEs, the primary challenge is modulating the activation threshold and kinetic profile of the CD3-TCR complex through precise epitope selection and conformational control. Utilizing the full TCR-CD3 complex for drug design and affinity optimization is far more effective for ensuring functional accuracy and safety. This approach helps mitigate off-target effects and prevents excessive T-cell stimulation caused by CD3 cross-linking, ultimately allowing for the decoupling of CRS (Cytokine Release Syndrome) from therapeutic anti-tumor toxicity.

Comparing VLP and Nanodisc Platforms

Due to the structure of VLP, strong immune response can be stimulated in animal immunization experiments. Their ability to present multiple copies of an antigen in a highly organized and repetitive manner makes them a particularly strong immunogen for such animal immunization experiments. When the VLP is used to immunize an animal, such as a rabbit or a mouse, a strong and rapid immune response will be elicited, leading to the production of high-titer antibodies. These antibodies can then be harvested and screened for a variety of research and therapeutic applications.

This high immunogenicity and safety profile make VLPs an ideal platform for generating a diverse and robust antibody response for research and discovery purposes.

Figure 1. Structure of multipass transmembrane proteins on a Virus-Like Particles (VLP)

Nanodiscs are membrane-mimetic structures composed of a phospholipid bilayer and membrane scaffold proteins. KACTUS leverages a detergent-free production process to produce SMA-based nanodiscs to maximally maintain the native structure and conformation of the full-length, multi-pass transmembrane proteins in soluble format, allowing wide applications in drug screening, analytical assay development and testing. With KACTUS Nanodisc products, precise evaluation of the kinetics can be determined.

Figure 2. Multipass transmemebrane protein on Nanodisc

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