All Times Shown in PST

7:00 am Morning Networking Coffee

7:20 am Chair’s Opening Remarks

  • Ismael Samudio Senior Director Cancer Biology & Translational Science, Notch Therapeutics

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

  • Erin Trachet Associate Director, Scientific Development, Labcorp Oncology

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

  • Viswanathan Muthusamy Director, Center for Precision Cancer Modeling & Research Scientist, Yale University

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

  • Mark Orr Senior Principal Scientist, ImmunoOncology & Cellular Therapy, Bristol Myers Squibb
  • David Messenheimer Senior Scientist, Pharmacology, Zymeworks

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

2:30 pm Chairs Closing Marks & End of Summit