Pre-Conference Bootcamp
NK Cell Biology Bootcamp
Tuesday, March 23
10.30 - 4.00 EDT | 07.30 - 1.00 PDT - All times shown in EDT
10:30 am Online Registration & Virtual Coffee Networking
10:30 am Online Registration & Virtual Coffee Networking
11:00 am Super-Charged Natural Killer Cells Target and Differentiate Cancer Stem Cells/Poorly Differentiated Tumors While Expanding CD8+ T Cells for Targeting of Differentiated Tumors; Studies of Cancer Patients and Humanized Mice
11:00 am Super-Charged Natural Killer Cells Target and Differentiate Cancer Stem Cells/Poorly Differentiated Tumors While Expanding CD8+ T Cells for Targeting of Differentiated Tumors; Studies of Cancer Patients and Humanized Mice
Synopsis
• In cancer patient derived tumors, NK cells bind and interact with stem-like tumors within the tumor microenvironment
• Analyze super-charged NK cells which have significantly increased capacity to target cancer stem cells/poorly differentiated tumors in 2D and 3D tumorospheres, and drive differentiation of stem cells within tumorospheres
• Discuss how, unlike activated primary NK cells, super-charged NK cells do not become inactivated after interaction with tumors within the tumorospheres, thus mediating serial killing
11:30 am Dynamics of Vg9Vd2 T Cells Cytotoxicity
11:30 am Dynamics of Vg9Vd2 T Cells Cytotoxicity
Synopsis
• Describe expansion and phenotypic evolution of Vg9Vd2 T cells from peripheral blood
• Outline a microchip platform for live-cell imaging of thousands of individual cells within larger populations and show how we use it to assess heterogeneity in cytotoxic response and serial killing by gamma delta T cells
• Share imaging-based assessment of the cytotoxic mechanisms used by gamma delta T cells
12:00 pm Morning Refreshments
12:00 pm Morning Refreshments
12:30 pm Discussion Session: What Is the Role of Inhibitory Receptors?
12:30 pm Discussion Session: What Is the Role of Inhibitory Receptors?
1:00 pm Understanding the Biology and Molecular Program NK Cell Memory
Synopsis
• Outline the critical understanding of memory and memory-like NK cells and their attributes
• Review distinct types of NK cell memory and memory-like responses
• Present the current understanding of the molecular program of memory-like NK cells
• Relate recent pre-clinical work supporting memory-like NK cells in solid tumors
1:00 pm Understanding the Biology and Molecular Program NK Cell Memory
1:30 pm Single-Cell Transcriptomics of Human NK Cells
1:30 pm Single-Cell Transcriptomics of Human NK Cells
Synopsis
• Single-cell transcriptome reveals significant heterogeneity within the bone marrow-derived human NK cells, grouped into
six major unique subsets
• The functionally mature CD57+ NK cells are marked with high expression of CX3CR1, HAVCR2 (TIM 3), and ZEB2, demonstrating unique transcriptional features. Adaptive (‘memory’) NK cells express a unique transcriptomic profile along with the high expression of NKG2C
• Explain how the transcriptomic profiles NK clusters, pseudotime trajectory of developmental progression, and the identification of major regulons offer exceptional new insights essential for NK cell based immunotherapies
2:00 pm Refreshment Break
Synopsis
Time to message those you would like to connect with using the online chat function, or simply take some time away from the screen to rest your eyes!
2:00 pm Refreshment Break
2:30 pm Genetic Manipulation of Chemotactic Receptors as a Novel Strategy to Modulate the Homing of Adoptively Transferred Ex Vivo Expanded NK Cells
Synopsis
• Ex vivo expansion of NK cells with feeder cells induces transcriptional shifts in thousands of protein coding genes
• Expanded NK cells have significant alterations in chemokine receptors (CRs) including downregulation of CXCR4 and upregulation of CCR5 and other CRs which may lead to preferential NK cell trafficking to the liver rather than the bone marrow
• Genetic modification of chemotactic receptors through transfection with CXCR4 mRNA and/or CRISPR/Cas-9 disruption of CCR5 can be used to redirect the cellular homing of adoptively infused NK cells in vivo to their desired tissue target
2:30 pm Genetic Manipulation of Chemotactic Receptors as a Novel Strategy to Modulate the Homing of Adoptively Transferred Ex Vivo Expanded NK Cells
3:00 pm NK Cell Activation in the Tumor Microenvironment
Synopsis
• Overview of the NK cell – cancer immunity cycle
• Highlight emerging strategies to therapeutically modulate NK cell activity in cancer
• Drugging cancer cells to convert ‘cold’ tumours into ‘hot’ tumours
3:00 pm NK Cell Activation in the Tumor Microenvironment
3:30 pm Innate Cell Engagers (ICE®) to Trigger Innate Immunity to Fight Cancer
Synopsis
– Review pre-clinical and clinical development of Innate Cell Engagers (ICE®), derived from the Redirected Optimized Cell Killing (ROCK®) platform
– Present the current development landscape of ICE® in hematological and solid cancer
– Present recent pre-clinical in vitro and in vivo work demonstrating efficacy and novel insights into the mode-of action of ICE® triggering Antibody-Dependent Cellular Cytotoxicity (ADCC) and Antibody Dependent Cellular Phagocytosis (ADCP)
– Provide preclinical foundation and future perspective to combine ICE® and adoptive cellular NK cell therapy (“in-situ-CAR-NK”) to treat cancer patients