*All Times Shown in PST
8:30 am Chair’s Opening Remarks
Bridging the Gap Between Pre-Clinical Tumor Models & Translational Research in IO
8:40 am Use of Human Knock-in Mice for Selecting New Generation of Immune Checkpoint Inhibitors
Synopsis
• How to select the best human knock-in mouse model for a specific project
• Tumor models and analysis of the immunological response in human knock-in mice
• Can human knock-in mice be used for PK analysis?
9:10 am Patient-Derived Tumor Xenografts in Humanized NSG-SGM3 Mice: A New Immuno-Oncology Platform
Synopsis
• The addition of 3 human cytokines (GM-CSF, IL-3 & Kit Ligand) into the NSG mouse provides for a more robust myeloid compartment after humanization
• Showcase data on the myeloid engraftment kinetics and also show checkpoint inhibitor efficacy against several PDX
• Leverage humanized mice to assess the risk of immunotherapeutic-associated cytokine release syndrome (CRS)
9:40 am Efficacy and irAE Assessment of Therapeutic Antibodies with Target Specific Knock-In Models
Synopsis
• Use of humanized genetically engineered mouse models (huGEMM) to look at efficacy of immune modulatory therapeutics
• Initial pre-clinical assessment of irAE using huGEMM models
10:10 am Understanding Toxicity in IO & Utilizing This to Create A Bigger Therapeutic Window
Synopsis
• Understanding the implications of the similarities between tumors and our own immune system: are we doomed to experience toxicity?
• Targeting the weakest points in a patient’s cancer to counteract the problems of toxicity
• Maximizing your therapeutic window: having tumors of the right size and dosing of drugs
• Dealing with off-target effects and how this can affect your mode
10:40 am Structured Networking & Morning Coffee Break
Synopsis
Grab a morning coffee and enjoy this structured networking break to reconnect with fellow industry and academic experts.
11:10 am Panel Discussion: Generating Meaningful Data with Your IO Models
Synopsis
In this panel discussion, we will
• Discuss how to make agents that work perfectly in-vitro translate into a better drug in the clinic
• Explore gold standards and benchmarking what good indications are for translatability in the clinic
• Assess what good looks like for our tumor models
11:40 am Humanized Models Enabling Enhanced Clinical Relevancy & Translatability
Synopsis
• Immune checkpoint humanized mouse models: assessment of biologics efficacy and combo-therapy; importance of model design on overall model performances
• BRGSF-HIS hCD34+ reconstituted mice featuring human lymphoid and myeloid compartments: analysis of the human immune system and effector function
12:10 pm Predicting the Safety & Efficacy of Mouse Models
Synopsis
• Clarifying the differences between surrogate antibodies and your clinical candidate
• PKPD: understanding it’s importance and relevance in IO treatment
• Establishing how to determine dosing frequency and volume from your mouse models
• Measuring efficacy: determining mechanistic measures including surrogate endpoints in efficacy studies
12:40 pm Careful Use of Your Pre-Clinical Mouse Models for Translatability
Synopsis
Too many failures on mouse model directed clinical experiments – how to overcome this
• Exploring the importance of understanding human correlate of mouse biology
• MOA based translation – not just efficacy
• Evaluating that human immune/tumor models have limited value in understanding the biology
1:10 pm Networking Lunch
2:10 pm Influence of the Gut Microbiome Toward Preclinical Translation of Cancer Immunotherapy
Synopsis
• Key species of bacteria exist that influence preclinical efficacy in tumor models
• Pre-treatment regimens, such as antibiotics, need to be considered in most preclinical models as these can impact the endogenous microbiome and may impact clinical efficacy
• Not all microbiomes are created equal and the depth at which we sequence (16S, metagenomic, etc) is critical to align on to speak the same language across microbiome studies for biomarkers and possible treatment modalities
2:40 pm Orthotopic Patient-Derived-Xenograft Models Guide Individualized Precision Oncology Therapy
Synopsis
• Orthotopic PDX (O-PDX) models can be derived from needle or surgical biopsies
• In vivo pharmacology studies accurately predict patient response
• The O-PDX methodology provides a platform for autologous humanization and precision IO studies
2:55 pm Outlining Pros & Cons of Slower Growing Models That More Accurately Represent Human Tumor Growth Kinetics
Synopsis
• Slowing it down: what are the impacts of comparing human and mouse tumors that grow at different rates?
• Developing representative models that including slower growing models to resemble more closely what is going on in the human tumor
• Understanding the challenge of monitoring growth of tumors that develop at different rates
3:25 pm Aracari Biosciences’ Vascularized Micro Organ (VMO™) and Vascularized Micro Tumor (VMT™) Platforms Contain 3D, Fully Human Tissues That Are Supported By Living, Perfused Blood Vessels
Synopsis
• Molecules and/or immune cells are delivered through the vascularizedbsystem directly to these tissues
• Gene expression and drug responses in the VMO and VMT models closely align with in vivo dose response and gene expression data, whereas data from monolayer and spheroid cultures do not
3:40 pm Persistence and Anti-Tumor Efficacy of Allogeneic CAR-NK Cells in Humanized IL15 Mice
Synopsis
• Exploring NK cell persistence in JAX vs Taconic IL15 mice
• What is the persistence of NK cells from different NK donors?
• Delving into the anti-tumor efficacy of CAR-NK cells in vivo
4:10 pm Afternoon Networking Break & Poster Session
Creating Predictive Models for Tumor Heterogeneity
4:40 pm Organ On Chip: Facing the Complications of Intra & Inter-Tumor Heterogeneity
Synopsis
• Establishing better models for IO using organ on a chip
• Understanding the importance of the dynamic TME in primary and acquired cross-resistance
5:10 pm Roundtable: Addressing Heterogeneity When Using Organoids
Synopsis
• Exploring the use of orthotopic organoids and their advantages, but how do we face the time frame & growth kinetics issues
• Navigating paracrine effects: do organoids accurately represent responses we would see in the clinical environment & how important is interaction with other cells in the organism
• Do organoids represent the original tumor more closely than other tumor models?
• Analyzing the problem of metastasis in organoids
5:40 pm Chair’s Closing Remarks, End of Day One & Networking
5:45 pm Drinks Reception Hosted by The Jackson Laboratory
Synopsis
Join us at our drinks reception to network and connect with your fellow colleagues