8:45 am
Chair’s Opening Remarks

  • Anahid Jewett Professor & Director of Tumor Immunology Laboratory, UCLA School of Dentistry and Medicine

9:00 am
Tumor Microenvironment and NK Cell Therapy

9:00 am Investigating the Consequences of Co-Incubation of Freshly Isolated, Resting NK Cells with K562, CTV-1, Daudi and RPMI-8226 Tumor Cell Lines on the Phenotype, Cytokine Profile and Transcriptome of the NK Cells

Synopsis

  • Examining specific tumor-induced NK cell signatures
  • Highlighting the key signaling molecules exclusively affected by tumor-priming
  • Understanding tumor-specific NK cell responses in the tumor microenvironment

9:30 am Refinement of NK Cell Immunotherapy: Strategies to Unleash the Killer in a Suppressive Tumor Microenvironment

  • Lotte Wieten Department Head of Transplantation Immunology , Maastricht University

Synopsis

  • Preclinical data supporting the use of alloreactive NK cells as immunotherapy for breast cancer
  • Comprehensive analysis of the functional relevance of HLA and inhibitory receptors for NK cell alloreactivity in breast cancer
  • Development of combinational strategies to maximize the anti-tumor potential of NK cells in a suppressive tumor microenvironment in haematological- and solid tumors

10:00 am Distinguishing Undifferentiated Tumors from Differentiated Tumors

  • Anahid Jewett Professor & Director of Tumor Immunology Laboratory, UCLA School of Dentistry and Medicine

Synopsis

  • NK cells are the effectors of selection and differentiation of Cancer Stem Cells/ undifferentiated tumors in pancreatic, melanoma, glioblastoma, lung, breast and oral tumors
  • We have identified and characterized combination of surface receptor markers which distinguish stem-like/undifferentiated tumors from differentiated tumors and have used to identify the degree and effectiveness of patient NK cells in differentiation of tumors
  • Membrane bound and secreted forms of IFN-g and TNF-a from NK cells are key cytokines in limiting tumor growth through differentiation of the tumors
  • NK inactivation occurs at the pre-neoplastic stage of tumorigenesis and becomes more severe at the neoplastic stage due to both the genetic and environmental factors
  • Factors contributing to the dysfunctional state of cancer patients’ NK cells are lack of expansion of NK cells, severe decrease in NK cell cytotoxicity, decreased secretion of IFN-g by the NK cell and lack of ability of secreted IFN-g to differentiate tumors

10:30 am
Morning Refreshments & Networking

11:00 am NK Cells and the Solid Tumor Microenvironment: Lessons Learned and Translational Potential

  • Robin Parihar Assistant Professor of Pediatric Hematology- Oncology , Baylor College of Medicine

Synopsis

  • Understand the role of the tumor immune microenvironment in patients receiving adoptive cellular therapy
  • Discuss a novel xenograft model of the TME for understanding mechanisms that limit immune therapies in solid tumors
  • Characterize the differing roles of MDSCs, inhibitory macrophages, and Tregs of the TME in affecting adoptive cellular therapies

11:30 am Harnessing NK Cells to Improve T-Cell Targeted Immunotherapies for Solid Tumor and Hematologic Malignancies

  • Amir Horowitz Assistant Professor of Oncological Sciences, Ichan School of Medicine

Synopsis

  • Exploring the under-appreciated layer of complexity around HLA-E-mediated inhibition and regulation of NK cell functions in the tumor microenvironment
  • Examining the effects of HLA-E expression and presence or absence of KIR ligands on tumor cells on prognosis and survival of cancer patients across numerous settings of hematologic and solid tumor mali gnancies
  • Tumor response to immune checkpoint blockade therapies

12:00 pm Panel Discussion: Identifying Strategies to Improve Efficacy in Solid Tumor Trials

  • Amir Horowitz Assistant Professor of Oncological Sciences, Ichan School of Medicine
  • Anahid Jewett Professor & Director of Tumor Immunology Laboratory, UCLA School of Dentistry and Medicine
  • Mark Lowdell CSO, ImmuneBio Inc

Synopsis

  • Strategies to allow NK cells to cross barriers into solid tumors and overcome strong immunosuppressive environments
  • Do immune-regulatory cells impact NK and T cells in the same way?
  • Discuss the potential of downregulating TGF-beta to allow for greater NK activity

1:00 pm
Lunch & Networking

1:30 pm
Clinical Trial Case Studies

Synopsis

Hear updates on the most advanced clinical programs to discover how the application of NK cell therapies are being successfully utilized in the clinic.

2:00 pm An Allogeneic, Off-The-Shelf NK Cell Product Derived from Placental Hematopoietic

Synopsis

  • Clinical studies suggest that adoptive transfer of allogeneic natural killer (NK) cells represent a promising treatment for patients with hematological malignancies and solid tumors
  • Celularity is developing an allogeneic, off-the-shelf NK cell product that is derived from placental hematopoietic stem cells and exhibits substantial cytolytic activity against various cancer cell lines, primary AML and primary MM cells
  • Clinical and translational development of Celularity NK cell product will be discussed

2:30 pm Pre-Emptive Donor-Derived Natural Killer Infusion for Patients with High-Risk Multiple Myeloma, Lymphoma, or CLL

  • Noah Merin Assistant Professor, Cedars-Sinai Medical Center

Synopsis

  • Attempting to add-back mature donor NK and NK/T cells after PTCy to hasten NK immune recovery
  • Outlining the two separate pheresis sessions donors undergo
  • Methods to evaluate abundance of NK receptor ligands, NK phenotype, KIR expression and inhibitory/activating receptors

2:45 pm
Addressing NK Cell Expansion

3:00 pm NK Cell Stimulation Using Membrane Bound IL-21

Synopsis

  • Addressing the needed for an effective and robust methodology for efficient production of large doses of NK cells with high anti-tumor potency
  • NK cell stimulation for production of high dosages and repeat dosages of highly potent NK cells.
  • Advancing clinical development of NK cell therapeutics for treatment of AML in the near future

3:30 pm
Afternoon Refreshments

4:00 pm Addressing Contact-Dependent Factors that Promote NK Cell Development

  • Emily Mace Assistant Professor of Pediatrics, Columbia University

Synopsis

  • Human natural killer (NK) cell development is a poorly understood process, particularly the nature of cell-cell contacts that shape NK cell functional maturation
  • Understanding the contact-dependent factors that promote NK cell development will better inform the design of rational NK cell-based immunotherapy
  • Here I will describe recent findings that have advanced our understanding of the generation of NK cell heterogeneity and functional phenotypes using novel in vitro and ex vivo systems

4:30 pm Discussing the Impact of Different Factors on Successful NK Cell Cryopreservation

  • Dean Lee Professor of Pediatrics, Nationwide Children's Hospital

Synopsis

  • NK cells are difficult to cryopreserve, with poor recovery of viability and function under
    conditions that work well for other lymphocytes (e.g., CAR-T cells), which has limited their
    potential in adoptive immunotherapy
  • We will discuss the impact on successful NK cell cryopreservation of IL-21 signaling,
    cryopreservation media, freezing programs, and cell density
  • Data on biomarkers of successful cryopreservation and clinical data that demonstrate
    survival and functionality of cryopreserved NK cells

5:00 pm
Chair’s Closing Remarks

  • Anahid Jewett Professor & Director of Tumor Immunology Laboratory, UCLA School of Dentistry and Medicine

5:15 pm
Close of Summit