Here’s a structured FAQ collection for researchers investigating TIO antibodies in translational immuno-oncology, synthesized from peer-reviewed literature and patents:
Discrepancies often arise from tumor microenvironment (TME) heterogeneity. Strategies include:
TME Profiling: Single-cell RNA sequencing to identify stromal cell interactions .
Dosage Optimization: Pharmacokinetic modeling to align antibody half-life with tumor growth rates .
Control Experiments: Compare isotype antibodies and genetic knockouts (e.g., CRISPR-edited antigen-negative tumors) .
Resistance pathways include antigen loss, immune exclusion, and suppressive cytokine upregulation. Research methodologies:
Functional Screens: CRISPR-Cas9 libraries to identify resistance genes .
Multiplex Imaging: Spatial analysis of antibody penetration in tumor cores vs. margins .
Biomarker Correlation: Link PD-L1/CD8+ T cell ratios to antibody response .
Cross-Species Testing: Validate in humanized murine models (e.g., human XCR1 knock-in) .
Off-Target Screening: Phage display libraries to assess binding to unrelated epitopes .
Computational Modeling: Molecular docking simulations to predict paratope-epitope interactions .