PK assessment of TCE

Human‑relevant PK modeling to maximize TCE clinical success

Most T-cell engagers have a short half-life, which prevents sustained therapeutic activity. Consequently, TCEs are often engineered to include an albumin binder for extended half-life. To be able to reliably test the half-life extension, researchers need translatable models expressing physiological levels of hSA and hFcRn, an approach validated by Crescendo biologics:

Figure 1 : PK analysis of a T-cell engager (CB307) in genO-hSA/hFcRn vs NCG mice, treated with exogenous human albumin.

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Find out more about this data in this paper: Archer et al., Clin Canc Res (2024)

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Another strategy is to fuse TCEs to human albumin, which has a long half-life due to its interaction with FcRn, as shown by Mandrup and colleagues:

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Figure 2: PK analysis of light T-cell engager (LiTE) and LiTE fused to an albumin sequence with high affinity to FcRn (Albu-LITE-HB).

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Find out more about this data in this paper: Mandrup et al., Commun Biol (2021)

If you’d like more information regarding the genO-hSA/hFcRn model, the only model with a physiological expression of human albumin and hFcRn, you can find it here:

If you want to simultaneously test the PK and efficacy of your TCE, we have also developed a mouse model with humanized ε, δ, γ subunits of CD3 – the genO-panhCD3/hSA/hFcRn model.

We also have other models available for testing T-cell engagers:

• genO-panhCD3

• genO-hCD3ε

• genO-hCD28

• genO-panhCD3/hCD28  

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