NK Cell-Based Cancer Immunotherapy

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. As preclinical and clinical studies continue, there is a clear need to better understand the mechanisms underlying the regulation of NK cell phenotype and function within the tumor environment to accelerate the development of NK cell-targeting therapeutics.

 

Cambridge Healthtech Institute’s 3rd 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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Wednesday, September 26

7:00 am Registration Open and Morning Coffee

MODULATING NK CELLS FOR HIGHER SPECIFICITY AND POTENCY

8:00 Welcome Remarks

Ngoc Emily Le, PhD, Conference Producer, Cambridge Healthtech Institute

8:05 Chairperson’s Opening Remarks

Bahram (Bob) Valamehr, PhD, MBA, Vice President, Cancer Immunotherapy, Fate Therapeutics, Inc.


8:10 KEYNOTE PRESENTATION: Novel Strategies to Produce Better NK Cells to Treat Cancer

Jeffrey Miller, MD, Professor, Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota

We have developed a trispecific killer engagers (TriKE) platform to make NK cells antigen specific and enrich for a unique population of adaptive NK cells that kill better, mediate enhanced antibody-dependent cellular cytotoxicity, can resist immune suppression mechanisms and exhibit properties of immunologic memory. To overcome limitation of single cell infusions, a platform to deliver off-the-shelf NK cells derived from clonal, genetically modified induced pluripotent stem cells (iPSC) was developed. These strategies alone or in combination with checkpoint blockade are key to the future.

8:40 Pluripotent Cell-Derived NK Cells as a Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy

Bahram (Bob) Valamehr, PhD, MBA, Vice President, Cancer Immunotherapy, Fate Therapeutics, Inc.

I will discuss our progress towards translating a unique and effective strategy to create a renewable source of “off-the-shelf” engineered NK cells derived from a single-cell derived master pluripotent cell line. The derived master pluripotent cell line is banked, characterized and repeatedly applied to our stage-specific directed differentiation process to reproducibly and reliably generate NK cells. Preclinical data highlight the therapeutic value of pluripotent-derived NK cells including anti-tumor capacity, manufacturing reliability and preclinical efficacy.

9:10 Inhibition of MICA and MICB Shedding by Tumor Cells Elicits NK Cell-Mediated Tumor Immunity

Kai W. Wucherpfennig, MD, PhD, Professor and Chair, Cancer Immunology and Virology, Dana-Farber Cancer Institute; Professor, Neurology and Microbiology/Immunobiology, Harvard Medical School

We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevent loss of cell surface MICA/B by human cancer cells. These antibodies inhibit tumor growth in multiple fully immunocompetent mouse models and reduce human melanoma metastases in a humanized mouse model.

 

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

MODULATING NK CELLS FOR HIGHER SPECIFICITY AND POTENCY (CONT.)

10:25 NKTR-255: Accessing the Immunotherapeutic Potential of IL-15 for NK Cell Therapies

Saul Kivimae, PhD, In Vivo Pharmacology Function Lead, Nektar Therapeutics

IL-15 has long been recognized for its potential as an immunotherapeutic agent. Exploiting this potential has been challenging due to unfavorable pharmacokinetic properties. NKTR-255 is a novel polymer-conjugated IL-15 that shows prolonged plasma exposure and IL-15 pathway activation while retaining high affinity IL-15Rα binding. NKTR-255 treatment expands and sustains activation of NK and CD8 memory T cell populations. High level of NK cell dependent anti-tumor efficacy is demonstrated in NKTR-255 treated mouse models of tumor metastasis.

10:55 Engineering NK Cells for Enhanced Potency and Persistence

James B. Trager, PhD, Senior Vice President, Research and Development, Nkarta Therapeutics

NK cells form a first line of defense against cancer, and they can be effective mediators of cytotoxicity and adaptive immunity. Efforts to maximize their potential as cancer therapeutics are hampered by difficulty in expanding NK cells, relatively short in vivo persistence, and the ability of tumor cells to evade NK recognition. We will discuss recent progress in overcoming these barriers to successful therapeutic application of NK cells.

11:25 Engineered, Off-the-Shelf NK Cell Lines for Patient Specific Cancer Treatment

Hans Klingemann, MD, PhD, Vice President, Research & Development, NantKwest, Inc.

aNK and haNK have completed Phase I studies, taNK (her-2 CAR) for glioma is currently accruing patients. Further genetic modifications of the haNK platform include additional CARs as well as homing receptors and molecules that can positively affect the tumor microenvironment. The off-the-shelf character of these cells is reflected in the fact that they can be cryopreserved and irradiated in bulk and shipped to the treatment site overnight.

11:55 PANEL DISCUSSION: all speakers in the session

  • How to increase specificity through targeting modalities
  • How to ideally edit NK cells to augment anti-tumor function
  • How to select the ideal NK cell
  • Will NK cells ultimately become the perfect solid tumor targeting cells

12:25 pm Session Break

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Poster Viewing

CLINICAL DEVELOPMENTS OF NK CELL-BASED THERAPIES

1:50 Chairperson’s Remarks

Hans Klingemann, MD, PhD, Vice President, Research & Development, NantKwest, Inc.

1:55 Genetic Modification of NK Cells to Retarget and Sustain Anti-Tumor Activity in Patients with Multiple Myeloma

Evren Alici, MD, PhD, Head, Gene and Cell Therapy Group, Division of Hematology, Medicine, Karolinska University Hospital, Sweden

In this talk, I will comparatively discuss various strategies for NK cell gene modification, modulation of degranulation using small molecules, as well as decreasing NK cell time-to-next-kill via modulation of intracellular RNA sensing pathways. I will also discuss results of a first-in-man autologous ex vivo expanded NK cell clinical trial in patients with multiple myeloma which showed the cells to be safe with some signs of efficacy and an interesting manageable side effect.

2:25 NK Cell Subsets and Their Plasticity – Implications for Cell Therapy

Karl-Johan Malmberg, MD, PhD, Professor, Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Norway

In this talk, I will discuss new insights into the underlying mechanisms behind the functional diversification of human NK cells, including the formation of a molecular memory, evidence for subset plasticity and dynamic imprints caused by NK cell responses to cytomegalovirus infection. In terms of clinical translation, we are currently exploring new strategies to selectively expand such “adaptive” NK cells for cancer therapies.

2:55 Fuelling Robust Anti-Tumor NK Cell Responses

David Finlay, Assistant Professor, School of Biochemistry and Immunology, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland

For robust anti-tumour functions NK cells increase the uptake of cellular fuels and the flux through metabolic pathways. We have characterised these metabolic responses in activated NK cells, discovered the metabolic regulators involved and their importance for NK cell effector function. NK cells have profound metabolic defects in various disease states where NK cell functional responses are impaired. These discoveries have important implications for NK cell immunotherapies.

3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

CLINICAL DEVELOPMENTS OF NK CELL-BASED THERAPIES (CONT.)

4:05 Harnessing NK Cell Memory for Leukemia Immunotherapy

Rizwan Romee, MD, Member Faculty and Director, Haploidentical Donor Transplant Program, Oncology/ BMT and Leukemia Program, Dana Farber Cancer Institute, Harvard Medical School

We identified human cytokine induced memory-like cells induced by brief activation of conventional NK cells with IL-12 and IL-18. These memory-like NK cells have enhanced anti-leukemia responses and we recently completed first-in-human Phase I clinical trial of these memory-like NK cells in patients with advanced AML/MDS with very promising safety and efficacy signal. We are now working on several approaches to expand the use of these memory-like NK cells in combination with other novel agents in transplant and non-transplant settings.

DISCOVERY PLATFORMS AND TECHNOLOGIES FOR NK CELLS

4:35 Chairperson’s Remarks

Hans Klingemann, MD, PhD, Vice President, Research & Development, NantKwest, Inc.

4:35 Dynamic Analysis of Human Natural Killer Cell Response at Single-Cell Resolution

Tania (Tali) Konry, PhD, Assistant Professor, Pharmaceutical Sciences, Northeastern University

We have developed a high throughput droplet based microfluidic platform to investigate the key features of NK cells associated with rapid, slow or inactive tumor killing kinetics in NHL. We are working on identifying NK cell heterogeneity and bio-functional characteristics to discover novel drug combinations for NK cell dependent immunotherapy via an integrated droplet platform. We identified significant variability in NK-lymphoma cell contact duration, frequency, and subsequent cytolysis. We extended this technique to characterize functional heterogeneity in cytolysis of primary cells from b-NHL patients.

 

5:05 Interactive Breakout Discussion Groups - View Details

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.

Targeting Solid Tumors with NK Cells

Moderator: Dan Kaufman, MD, PhD, Professor, Director, Cell Therapy Program, University of California, San Diego

  • What antigen(s) are best to target?
  • CAR vs. antibody vs. NK cell engager strategies against solid tumors
  • How best to combine NK cells with other agents in clinical trials?

Addressing NK Cell Complexity in Clinical Trials

Moderator: Karl-Johan Malmberg, MD, PhD, Professor, Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Norway

  • Which subsets predict response?
  • Which phenotypes are generated by selection or expansion methods?
  • How to implement the emerging insights into the regulatory role of NK cells as a bridge to adaptive immunity?
  • How to address these questions systematically and consistently in clinical trials?

 

6:05 Welcome Reception in the Exhibit Hall with Poster Viewing

7:10 Close of Day

 

Thursday, September 27

7:30 am Registration Open and Morning Coffee

DISCOVERY PLATFORMS AND TECHNOLOGIES FOR NK CELLS (CONT.)

8:00 Chairperson’s Remarks

Hans Klingemann, MD, PhD, Vice President, Research & Development, NantKwest, Inc.

8:05 NK Cells and Glioblastoma

Michael A. Caligiuri, MD, President and Physician-in-Chief, City of Hope National Medical Center

Glioblastoma remains an incurable malignancy, presenting as late-stage disease with a very poor overall survival. Oncolytic viral therapy is currently being explored in clinical trials, but in some instances, natural killer (NK) cells present a barrier to effective viral replication and tumor lysis. We have discovered how NK cells “see” human herpes virus – a mechanism we have named Fc bridged cellular cytotoxicity – and have therefore devised strategies to circumvent this barrier for this deadly disease.

8:35 New Insights into Requirements for Human NK Cell Development

Emily Mace, PhD, Assistant Professor, Pediatric Immunology, American Society for Hematology Scholar, Pediatrics, Columbia University Irving Medical Center

In this talk, I will discuss recent developments in understanding the requirements for the differentiation and expansion of functionally mature human NK cells from immature precursors. In particular, I will focus on insights derived from in vitro differentiation systems that hold promise for better understanding and improving the efficiency and specificity of clinically relevant NK cell subsets.

9:05 Reports from Wednesday Evening Breakout Discussions

9:35 Coffee Break in the Exhibit Hall with Poster Viewing

DISCOVERY PLATFORMS AND TECHNOLOGIES FOR NK CELLS (CONT.)

10:20 Discovering Novel Therapeutic Antibody to Modulate NK Cells for Cancer Immunotherapy

Zhengmao Ye, PhD, Biochemical and Cellular Pharmacology, Genentech

Natural Killer cell is a critical immune cell subset mediating tumor killing. In this proposal, I plan to discuss a drug discovery project targeting a cell surface protein that mediates the suppression of NK and CD8+ T cell activity. I will discuss the functional assay development/antibody screening strategy for lead identification as well as pharmacological characterization of the lead molecule and its MOA elucidation.

10:50 Engineering Human Pluripotent Stem Cells to Produce NK Cells with Improved Targeted Anti-Cancer Activity

Dan Kaufman, MD, PhD, Professor, Director of Cell Therapy Program, University of California, San Diego

Our studies have designed novel chimeric antigen receptors optimized to enhance NK cell-mediated anti-tumor activity. We use human induced pluripotent stem cells (iPSCs) as a platform to express these NK-CARs and can efficiently produce iPSC-derived NK cells with stable CAR expression. NK-CAR-expressing iPSC-NK cells demonstrate improved anti-tumor activity in vitro and in vivo. We are now translating these NK-CAR-iPSC-NK cells to produce a standardized, targeted “off the shelf” anti-cancer immunotherapy.

11:20 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

11:50 Conference Registration Open


12:20 pm Plenary Keynote Program

2:00 Refreshment Break in the Exhibit Hall with Poster Viewing

2:45 Close of Conference


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