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TCR Engineering & Characterization

The development of TCR-based therapies faces key challenges, including the extremely low affinity of target TCR to peptide-MHC complex on tumor cells, which limits target recognition. Balancing affinity is critical, as high-affinity TCRs may reduce specificity, while low-affinity TCRs fail to activate T cells effectively. At ProBio, we overcome these challenges through the integrated TCR platform, including affinity maturation, in vitro functional characterization, and in vivo evaluation.

Features

Integrated TCR Solution

Affinity maturation
In vitro functional evaluation
In vivo pharmacology
Substantial Affinity Improvement

Effective affinity maturation platform to substantially improve affinity ( ~ 1800 fold)
Universal Assay Format High-throughput

Universal assay platform to allow a high-throughput for in vitro functional evaluation and specificity screening
Superior Assay Sensitivity

Superior assay sensitivity in detection of antigen independent T cell activation to mitigate the risk of off-target toxicity

TCR Affinity Maturation

General workflow of TCR affinity maturation

Binding validation of TCR on phage platform
Consecutive NNK library construction
Library panning and screening
Recombinant expression in mammalian cell for validation and characterization

TCR In Vitro Functional Characterization

Items	Service type	Main readouts
TCR KO Jurkat Reporter cell based assay (RGA)	Activation and specificity verification of TCR	Luminescence
Primary T cell based cytokine release	Cytotoxicity and specificity verification of TCR	Release of IFN-γ, TNFa, IL-2, IL-4, IL6, IL10 etc. from TCR-T cells upon co-culturing with pMHC cell
Primary T cell based cytotoxicity	Cytotoxicity and specificity verification of TCR	LDH, Luminescence
TCRxCD3 functional evaluation by RGA based on Jurkat line	Activation and specificity verification of TCRxCD3	Luminescence

TCR In Vivo Evaluation

Items	Service type	Main readouts
PBMC humanized xenograft models	In vivo efficacy	Tumor growth/weight inhibition
Xenograft models for TCR-T cell	In vivo efficacy	Tumor growth/weight inhibition
In vivo PK/persistence for TCRxCD3 bispecific or TCR-T cells	PK/bio-distribution	PK parameters: Cmax, Tmax, T1/2, AUC etc
Early toxicity	In vivo safety	Toxicology parameters: general observation, cytokine release, pathology etc