Unlocking Intracellular Targets: Drug Discovery with Fully Human TCR-Mimic Antibodies

Therapeutic antibodies have transformed cancer treatment, but conventional antibody modalities are largely limited to cell-surface and soluble targets, leaving more than 70% of the human proteome beyond their reach. T-cell receptor mimic (TCRm) antibodies expand the targetable space by recognizing intracellular targets when presented as peptides bound to human leukocyte antigen (pHLA) complexes. However, conventional TCRm discovery platforms that rely on synthetic libraries and in vitro affinity maturation frequently face challenges with unpredictable off-target cross-reactivity, leading to clinical safety liabilities. 

Biocytogen addresses this key industry bottleneck through its proprietary RenTCR mimic™ platform. By combining HLA-humanized RenMice® with high-throughput Beacon single-cell screening, the platform leverages natural in vivo negative selection to reduce the risk of self-reactive clones and bypass the need for artificial in vitro engineering. This approach enables the efficient discovery of fully human TCRm antibodies with broad sequence diversity, high affinities, and favorable biophysical and safety profiles. 

In this webinar, we will discuss: 

• How in vivo selection helps address off-target toxicity pitfalls in synthetic TCRm discovery. 
• Case studies and validation data across high-value intracellular targets, including WT1, KRAS G12V, and NY-ESO-1. 
• Versatile therapeutic applications, from bispecific/trispecific T-cell engagers (TCEs) to TCRm-T cell therapies targeting low antigen densities. 

Speaker

Yue Zhang, Ph.D., Project Manager, TCR Mimic Antibody Discovery 

Panelist:

Fengqian Chen, Ph.D., Regional Director, BD & Licensing 

Meng (Mona) Jiao, Ph.D., Sr. Scientist, Antibody Drug Discovery biocytogen.com