Tatiana Ort
Seminars
Thursday 16th October 2025
Panel Discussion: Investigating Preclinical Platforms for Autoimmune T-Cell Engagers From Human Relevant Assays to Regulatory Confidence
2:40 pm
- For TCEs in autoimmunity, conventional preclinical tools, often adapted from oncology, fall short in capturing the inflammatory, chronic, and tissue-specific nature of disease.
- This panel will explore how to build assays that reflect real autoimmune biology, capture safety-relevant signals, and avoid reliance on transgenic animals. With human target expression and immune context being essential, developers are rethinking how they model tissue penetration, subset-specific depletion, and chronic inflammatory responses e.g. for emerging modalities like gamma delta T-Cell engagers.
- Regulatory expectations are also evolving, and this session will address what evidence best supports safe and effective IND filings.
- Building disease-relevant in vitro systems that incorporate inflammatory cytokine environments to reflect autoimmune activation states
- Demonstrating selective target cell depletion and tissue or lymph node engagement in the absence of exaggerated cytokine release or off-target killing
- Replicating chronic, low-grade inflammatory contexts in preclinical assays to detect tolerability and null responses rather than acute cytotoxic triggers
- Evaluating the translational relevance of preclinical models, such as for gamma delta T-cell engagers and define how to justify safety and efficacy without conventional animal studies
Thursday 16th October 2025
Engineering the Next Generation of T-Cell Engagers Through Selective Activation to Improve Specificity, Potency & Safety
10:00 am
- Advancing beyond first-generation TCEs by unpacking the rationale behind engineering trispecific molecules to selectively engage CD8+ T-cells and how this improves specificity and reduces off-target activity in autoimmune disease
- Designing conditional activation for enhanced safety: Explore how activity restricted to target-bound TCEs helps minimize unwanted immune activation and cytokine release, with implications for autoimmune disease therapy
- Comparative engineering strategy: Contrasting AstraZeneca’s novel TCE architecture against first-generation engagers and competitor approaches, highlighting how molecular design choices influence preclinical performance and translational potential
