2017 Archived Content
While a large portion of cancer immunotherapies focus on targeting T cells, there has been a surge of interest in harnessing the relatively underexplored natural killer (NK) cell system for therapeutic intervention. A growing number of studies into pathways elucidating NK cell biology, activating and suppressing NK cell function, the development of pharmacological and genetic methods to enhance NK cell anti-tumor immunity, and the ability to expand NK cells ex vivo have set the stage for a new generation of cancer immunotherapies.
Cambridge Healthtech Institute’s 2nd Annual NK Cell-Based Cancer Immunotherapy conference will once again convene immuno-oncology researchers, cancer immunotherapy developers, and technology providers to discuss current challenges and opportunities, from discovery NK immuno-oncology to clinical studies, share latest technologies and development approaches, as well as to provide updates on preclinical, clinical, and combination studies.
Final Agenda
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Tuesday, September 26
7:00 am Registration Open and Morning Coffee
8:00 Welcome Remarks
Kip Harry, Senior Conference Director, Cambridge Healthtech Institute
8:05 Chairperson’s Opening Remarks
Karl-Johan Malmberg, M.D., Ph.D., Professor, Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital
8:10 KEYNOTE PRESENTATION: Novel Ways to Target and Activate NK Cells to Treat Cancer
Sarah A. Cooley, M.D., Associate Professor, Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota
We have discovered a new subset of NK cells termed adaptive with properties of immunologic memory induced by cytomegalovirus, which we think has potent anti-tumor activity. These cells exhibit enhanced anti-tumor activity in vitro and in vivo. We have recently developed a method to expand these cells from CMV seropositive donors and are testing this product in clinical trials. Lastly, NK cells can be made antigen specific to target tumors through IL-15 tri-specific killer engagers (TriKEs) to enhance the activity of NK cells in the clinic.
8:40 Update: aNK and haNK for Cancer Treatment
Hans Klingemann, M.D., Ph.D., Vice President, Research & Development, NantKwest, Inc.
I will provide an update on clinical trial activities with aNK haNK cells expressing the high affinity Fc-Receptor for combination therapy with mAbs taNK cells engineered to express CARs for neo-epitopes. I will also discuss augmenting NK activity with IL-15 super-agonist Altor 803, as well as optimizing NK target activity through CRISPR-based gene manipulation.
9:10 hnCD16-NK Cells: Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy
Bahram (Bob) Valamehr, Ph.D., MBA, Vice President, Cancer Immunotherapy, Fate Therapeutics, Inc.
Through targeted transgene integration, we produced a clonal pluripotent cell master cell line to continuously produce NK cells engineered to uniformly express a novel high affinity, non-cleavable version of CD16 Fc receptor (hnCD16-NK). Preclinical data highlight the therapeutic value of hnCD16-NK cells as an ideal ADCC-mediated “off-the-shelf” NK cell-based immunotherapeutic product with augmented persistence, anti-tumor capacity, manufacturing reliability and preclinical efficacy.
9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:25 Tetravalent Bispecific NK Cell-Engaging Technology for the Activation of Innate and Adaptive Immunity in Cancer
Martin Treder, Ph.D., CSO, R&D, Affimed
Affimed has developed a pipeline of clinical & preclinical stage NK cell engagers; they are CD16A-specific tetravalent, bispecific antibodies, characterized by high-affinity, specific binding to CD16A and superior NK cell retention compared to conventional antibodies. Strongly differentiating them from marketed therapeutic antibodies is the virtual lack of interference by circulating IgGs. Our NK cell platform has been shown to be safe and to act synergistically in combination with checkpoint modulators, activating both innate and adaptive immunity.
10:55 NK Cell Activation, Desensitization and Inhibition: Approaches to Mobilize NK Cells for Cancer Immunotherapy
David H. Raulet, Ph.D., C.H. Li Professor of Immunology and Pathogenesis; Co-Chair, Department of Molecular and Cell Biology, University of California, Berkeley
Mechanisms of NK inhibition and desensitization will be discussed. Approaches to reverse inhibition and desensitization for cancer therapy will be presented. Importantly, NK cells must be activated in order to target tumor cells. Activation of NK cells requires engagement of activating receptors on NK cells and cues from the innate immune system. Immunotherapeutic approaches being developed by Dragonfly Therapeutics to activate NK cells and target them to tumors will be discussed.
11:25 Discovery and Validation of Novel NK Cell Checkpoints
Jai Rautela, Ph.D., CSO & Co-Founder, oNKo-innate
The description of ‘a balance of activating and inhibitory signals’ is a necessarily vague understanding of how an NK cell makes the decision to kill a target cell. From this, it appeared that a complex immunotherapeutic strategy would likely be required to improve the anti-tumor function of NK cells. By performing a combination of genetic and small molecule screens we have begun to unravel the major druggable pathways the regulate NK cell function. Our recent discovery of a novel cytokine-induced checkpoint (‘CIS’) has highlighted the efficacy of these approaches, and suggested that there may, in fact, be relatively few unifying pathways that we can target to improve endogenous or adoptive NK cell function.
11:55 Rapidly Characterizing and Verifying Immunological Cell Populations Using Alpha and LANCE TR-FRET Technology
Jeanine M. Hinterneder, Ph.D., Applications Scientist, PerkinElmer
In the quest to develop new strategies to selectively expand tumor reactive NK cells for cancer immunotherapy, there is a need for more rapid, reliable assays to verify and quantify characteristic biomarkers expressed in these populations. At PerkinElmer, we provide a myriad of tools for rapidly measuring proteins expressed in multiple cell populations, with AlphaLISA and LANCE TR-FRET kits designed to quantify immunotherapy targets like CTLA-4, CD-28, CD-80, PD-1, and PD-L1 as well as cytokines crucial for NK cell development and proliferation, such as IL-15 and IL-21. For examining the mechanisms of action (MOA) of potential therapeutic antibodies, we offer a variety of binding assays, including two kits for probing analyte affinity for the FcyR3A (CD16A) receptor (either high or low affinity isoforms). Downstream signaling pathways can be studied further using our large selection of Alpha SureFire Ultra kits for measuring phosphorylation events, such as our kits for measuring STAT activity (e.g., p-STAT-3 and total STAT-3) and SLP-76 phosphorylation. Additionally, because these assays are highly sensitive, only small sample volumes are required, so multiple targets can be measured from a single well.
12:25 pm Enjoy Lunch on Your Own
1:15 Refreshment Break in the Exhibit Hall with Poster Viewing
1:50 Chairperson’s Remarks
Hans Klingemann, M.D., Ph.D., Vice President, Research & Development, NantKwest, Inc.
1:55 Functional Diversification of Human NK Cells - Implications for Cell-Based Cancer Immunotherapy
Karl-Johan Malmberg, M.D., Ph.D., Professor, Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital
In this talk, I will discuss new insights into the underlying mechanisms behind the functional diversification of human NK cells, including the dynamic imprints caused by NK cell responses to cytomegalovirus infection. In terms of clinical translation, we are currently exploring new strategies to selectively expand tumor reactive NK cell subsets for cancer immunotherapy.
2:25 Utilizing Immunostimulatory Cytokines to Unleash Natural Killer Cell Anti-Tumor Responses
Todd A. Fehniger, M.D., Ph.D., Associate Professor, Medicine, Division of Oncology, Washington University School of Medicine
Memory-like NK cells exhibit enhanced functional response to leukemia and other malignancies in vitro and in vivo, and recently have shown promise in a first-in-human early phase clinical study for patients with acute myeloid leukemia. IL-15 receptor super agonist complexes provide in vivo endogenous IL-15 receptor trans-presentation, and may be harnessed to support the expansion and functional capacity of NK cell in cancer patients. Thus, cytokine function-enabled NK cells represent an innovative translational immunotherapy approach for cancer patients.
2:55 Profiling How Immune Inhibitors Secreted by Melanoma Affect NK & Other Immune Cells
Anton Yuryev, Ph.D., Consulting Director, Biology, Research & Development, Elsevier
Understanding how cancer cells inhibit the local immune response is fundamental to selecting the best targets for immune-based therapies. A simplified workflow that incorporates disparate information sources and that helps provide connected, integrated data to support target selection will be presented, using immune cells suppressed by secreted melanoma proteins.
3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced
4:05 Adoptive Immunotherapy with Expanded NK Cells - The Impact of STAT3 Signaling and Crosstalk with Adaptive Immunity
Dean Anthony Lee, M.D., Ph.D., Professor, Pediatrics; Director, Cellular Therapy and Cancer Immunotherapy Program, Nationwide Children’s Hospital; James Comprehensive Cancer Center/Solove Research Institute, The Ohio State University
We developed a system for ex vivo NK cell expansion based on genetically modified feeder cells expressing IL-21, which through STAT3 signaling induces robust activation and proliferation of NK cells from normal donors, patients, cord blood, and embryonic/pluripotent stem cells. We established the GMP infrastructure to manufacture clinical-grade NK cells using this approach, and infused expanded NK cells into patients as monotherapy, in single or repeated infusions, or in combination with chemotherapy or stem cell transplantation.
4:35 Immune Responses in the Cancer Patients Who Receive the Random Donor-Derived Expanded NK Cell
Sungyoo Cho, Ph.D., CSO, Green Cross LabCell
Ex vivo-expanded and highly activated NK cells from random unrelated healthy donors injected into patients with malignant lymphoma or advanced recurrent solid tumors with or without lymphodepletion. Different from CAR-T treatment, there is no SAE and cytokine storm in multiple high dose injection. NK cell treatment shows different from T cell therapy in GvHD/GvT aspect. NK cell persistency and efficacy can control by pre-treatment regimen, and the rejection and antibody induction from recipients can also be controlled.
5:05 Interactive Breakout Discussion Groups
Join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Details on the topics and moderators are below. Please click here for full details on all breakouts.
Off-the-Shelf Cancer Immunotherapy
Moderator: Bahram (Bob) Valamehr, Ph.D., MBA, Vice President, Cancer Immunotherapy, Fate Therapeutics, Inc.
- Genetic engineering of pluripotent cells
- Derivation and expansion of single pluripotent cell clones
- Generation of off-the-shelf NK and T cells
Addressing NK Cell Complexity in Clinical Trials
Moderator: Dean Anthony Lee, M.D., Ph.D., Professor, Pediatrics; Director, Cellular Therapy and Cancer Immunotherapy Program, Nationwide Children’s Hospital; James Comprehensive Cancer Center/Solove Research Institute, The Ohio State University
- Which subsets predict response?
- Which phenotypes are generated by selection or expansion methods?
- How to address these questions systematically and consistently in clinical trials
6:05 Welcome Reception in the Exhibit Hall (Sponsorship Opportunity Available)
7:10 Close of Day
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Wednesday, September 27
7:30 am Registration Open and Morning Coffee
8:00 Chairperson’s Remarks
Bahram (Bob) Valamehr, Ph.D., MBA, Vice President, Cancer Immunotherapy, Fate Therapeutics, Inc.
8:05 Autologous ex vivo Understanding of NK Cell Effector Functions: A Single-Cell Lab-on-a-Chip Perspective
Tania Konry, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, Northeastern University
Natural Killer (NK) cells are an essential component of innate immunity that actively inhibit tumor development. Here we present a novel single-cell method of analyzing the mechanisms underlying the cellular interactions of NK cells with multiple myeloma cells. The integrated droplet microfluidics device developed by our group permits compartmentalization of cell pairs and secreted products within sub-nanoliter volumes and thereby controls cell-to-cell communication by limiting it to interactions between the co-encapsulated cells. It allows monitoring of both contact-dependent (immune synapse formation, delivery of lytic hits) and contact-independent cellular interactions (release of cytokines, chemokines) simultaneously. This dynamic single-cell experimental model is expected to provide preclinical information particularly relevant to the scenario of NK cell-cancer cell interactions.
8:35 oNKord® – Genetic Update – From Proven Safety to Established Efficacy
Jan Spanholtz, Ph.D., CSO, Glycostem
Glycostem Therapeutics is developing allogeneic cellular immunotherapy to treat various types of cancer. Glycostem’s patented industrial applicable production platform technology enables the generation of a multitude of products like expanded stem cells, NK cells, dendritic cells and genetically modified versions of those. The universal allogeneic treatment principle, allowed by the unrestricted use of immune cells in various types of cancer, is enabled by unlimited source of cord blood stem cells.
9:05 Selected Poster Presentation: IL-15 Infusions in Cancer Patients Induce Expansions of Cytotoxic CD56bright NK Cells with Increased Cytokine Release Capabilities
Sigrid P. Dubois, Ph.D., Staff Scientist, Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute
9:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:20 SPEAKER CANCELLATION: Expansion of NK Cells
Eun Young Choi, Ph.D., Researcher, Laboratory, IMMUNISBIO
With 60 cc of patient’s peripheral blood, more than 5 billion immune cells can be cultured. The cultured immune cell would consist of 60% natural Killer cell (NK cell) and NKT cell and 40% T cell. With autologous and cytotoxic characteristics of NK cell, it can be effectively used in treating cancer without side effects.
10:50 Autologous ex vivo Expanded NK Cells for Solid Tumor Immunotherapy
Ali Ashkar, D.V.M., Ph.D., Professor, Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University
Recent advances in NK cell expansion and activation have generated renewed interest in adoptive NK cell therapy for cancers. We have expanded NK cells from blood of breast, lung and ovarian cancer patients and have investigated their activities against autologous primary tumor cells. In addition, we have established xenograft models with the primary tumors to study the anti-tumor activities of autologous NK cells against primary tumor cells in vivo. Ex vivo expanded NK cells survive and proliferate in vivo in the presence of autologous PBMCs.
11:20 Enjoy Lunch on Your Own
12:35 pm Plenary Keynote Program
(click here for details)
2:00 Refreshment Break in the Exhibit Hall with Poster Viewing
2:45 Close of Conference
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