All Times Shown in PST
7:00 am Morning Networking Coffee
7:20 am Chair’s Opening Remarks
Expanding Your Pre-Clinical Model Toolbox
7:30 am Keynote: T Cell Based Therapies: Outlining Strategies for Enhanced T Cell Activation & Overcoming T Cell Exhaustion
Synopsis
• Suboptimal T cell activation and T cell exhaustion enables rapid tumor development: understanding the points in which T cell activation and exhaustion can be controlled
• Using IO therapies to enhance T cells function in the tumor microenvironment
• Exploring the lineage commitment of T cells as they progress towards terminal exhaustion: preventing versus reversing exhaustion
8:00 am Seeing Your Tumor & Other Things: Advanced Imaging for Preclinical Studies
Synopsis
• Recognizing the value of imaging to pharmaceutical R&D
• Examples from optical, MR and PET imaging will be reviewed
8:30 am Assessment of Preclinical Biomarkers for T cell Activation & Anti-Tumor Responses in the TME Following Radiation Therapy
Synopsis
• Overview of different biomarkers and their functions
• Preclinical immuno-oncology models and biomarkers
• Brief discussion of biomarkers in immuno-oncology clinical trials
8:45 am Virtual Speed Networking & Morning Break
9:30 am Panel Discussion
Synopsis
• Discuss model selection for bispecific vs T-cell engager vs small molecule vs ADC
10:00 am Syngeneic Metastasis Models & Patient Derived Ex Vivo Models for Preclinical Applications
Synopsis
• Progress with syngeneic metastasis models in immuno-oncology
• What have we learned?
• Patient derived ex plant models – do they work in investigation of IO agents?
• Assessing the criteria for choosing these models
Maximizing Your Model Predictability
10:30 am Exploring In Vitro Assays & The Innate Immune Response
Synopsis
• Focusing on the innate immune response to develop more predictive models
• Establishing immune phenotype screening that translates in vivo
Deep Diving Into Preclinical Combination- IO Therapies
11:00 am PD-L1 Blockade Restores CAR T Cell Activity Through IFNγ-regulation of CD163+ Macrophages
Synopsis
| – Modeling macrophage-mediated immune suppression of CAR T cells in vitro
– CAR T cells modulate immune-suppressive macrophages – Combination of CAR T cells and anti-PD-L1 antibody therapy reverses macrophage-mediated immune suppression |
11:30 am Fireside Chat
Synopsis
• Evaluating combination-IO therapy strategies and how to appropriately model them
12:00 pm Networking Lunch & Poster
Evaluating the Importance of the Dialogue Between Cells & Challenges Faced When Modelling the TME
1:00 pm Evaluating & Addressing the Challenges of the TME in multiple Solid Tumor CAR T Cell Models
Synopsis
• The use of cyclophosphamide to modulate the suppressive TME in syngeneic mouse models to improve solid tumor CAR T cell therapy
• Using syngeneic models to properly identify potential of immune-modulators in combination with solid tumor CAR T cells
• Developing alternate murine CAR T cells and mouse tumor models expressing relevant tumor antigens found in human cancers
1:30 pm The Tumor Support Network: Stromal Compartment of TME
Synopsis
• Highlighting the importance of stromal compartment and naïve components of the immune system which have specialized roles in supporting the tumor
• Discussing how syngeneic models are lacking in their stromal compartment which does not accurately reflect human tumors
• Can we develop models to recapitulate the immune and stromal contexture of solid tumors to predict efficacy of I/O combinations in the clinic?
2:00 pm Unravelling the Tumour Microenvironment: Hypoxia Induced HIF-1a Expression in NK Cells Promotes Anti-Tumor Effector Functions
Synopsis
• Hypoxia in the TME is a major contributor to immune evasion in solid tumours. Whether HIF-1α is expressed in hypoxic NK cells in the context of IL-2 and if its expression regulates NK cell effector function was studied
• Human NK cell line NKL and ex vivo expanded NK cells
• expressed HIF-1α upon IL-2 stimulation in hypoxia and exhibited improved antitumour cytotoxicity and IFN-g secretion
• Ex vivo expanded human NK cells and NKL cells required the concerted activation of PI3K/mTOR pathway initiated by IL-2 signalling in combination with hypoxia for HIF-1α stabilization