Predictive Tumor Models to Accelerate Your Preclinical Research in Vivo, in Vitro and in Silico
Thursday, April 11, 2024
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Chapters
Introduction
PDX a gold standard in preclinical research
mPatient Derived Xenograft - PDX
PDX Preserve Tumor Architecture
PDX Represent (largely) the Molecular Landscape
PDX of hematological malignancies
Breadth and depth of PDX Collections
Model Selection for Drug Testing
PDX and the Tumor Microenvironment
Tumor biology and microenvironment
PDX material as cell source for in vitro assays
PDX-derived cell lines - in vitro versus in vivo
In vitro screening for in vivo candidate selection
The need for a more relevant Tumor microenvironment (TME)
Speaker: Kolin C. Hribar
Three immune phenotypes
3D organoid / tumor models for recreating the TME
The ideal 3D tumor model platform
Application of 3D in vitro models in drug discovery
PDX in vivo models contain mouse, not human, fibroblasts
Cypre platform: 3D tumor microenvironment models
3D ex vivo tumor model screening
Overview of different read-outs
Case Study: screening T cell engager in 3D PDX models
Case study: checkpoint inhibitor combination in NSCLC
In vitro vs in vivo correlation pharmacology data
PDX based in vivo formats-Julia
PDX for Drug Development
In vivo Screening
Single Mouse Trial Format
Single Mouse Trial (SMT)
Cytotoxic and targeted drug testing in SMT format
Interpretation of SMT data
PDX and the Tumor Microenvironment
Optical Imaging for PDX
Brain Tumor SMT Design
High Grade Glioma Models
Evaluate new modalities using PDX
PDX and the Tumor Microenvironment
Humanized models in NOD-SCID-IL2R null mice
In depth characterization of 14 NSCLC PDX models
TIL rate determined by FC
In vivo study design CAR T cells
Translatable CAR-T models
In vivo screening approach for combination testing
Tumor killing and modification of TIL landscape
Transcriptomic analysis identified LXH255 and Sunitinib as ICD inducers
PDX going in silico
What if we could predict response, determine mechanisms of acquired resistance, and identify combo therapies all without the use of animal models?
Genetic circuitry in cell replication of cancer
Why is the time now?
Trends in human multi-omic data have reached a tipping point
There has been an exponential growth in computing power
AI shifts gears; causal AI emerges
What are Gemini Digital Twins?
How Aitia uses the Gemini Digital Twins to simulate billions of ‘experiments’ to discover novel drug targets and biomarkers of response
Gemini Digital Twins Towards Trial Simulation and Patient Selection
PC Gemini Digital Twins Validation
PTCH1 germline mutation predicts enzalutamide resistance
PDX Digital Twins to simulate billions of ‘experiments’ to determine the optimal tumor type and impact of drug on tumor size
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