Cambridge Healthtech Institute’s Inaugural

Targeting Innate Immune Cells

Harnessing Natural Killer, Macrophage and Dendritic Cells for New Cancer Immunotherapies

December 5-6, 2017 | Hilton San Diego Resort | San Diego, CA


While a large portion of cancer immunotherapies focus on targeting T cells, there has been a surge of interest in harnessing the relatively underexplored innate immune system for therapeutic intervention, with particular focus on natural killer (NK) cells, macrophages and dendritic cells. A growing number of studies into pathways elucidating innate cell biology, and the development of therapeutic agents to activate or suppress cell function, have set the stage for a new generation of cancer immunotherapies.

Cambridge Healthtech Institute’s Inaugural Targeting Innate Immune Cells conference will convene immuno-oncology researchers, cancer immunotherapy developers, and technology providers to discuss current challenges and opportunities, from discovery 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

TUESDAY, December 5

7:30 am Registration and Morning Coffee

ADVANCES IN NK CELL-BASED THERAPIES

8:30 Chairperson's Opening Remarks

Hans Klingemann, M.D., Ph.D., Vice President, Research & Development, NantKwest, Inc.

8:35 Update: aNK and haNK for Cancer Treatment

Hans KlingemannHans 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.

9:20 hnCD16-NK Cells: Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy

Bahram ValamehrBahram (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.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 Autologous ex vivo Understanding of NK Cell Effector Functions: A Single-Cell Lab-on-a-Chip Perspective

Tania_KonryTania 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. 

11:20 KEYNOTE PRESENTATION: Engineering Human Pluripotent Stem Cells to Produce NK Cells with Improved Targeted Anti-Cancer Activity

Kaufman DanDan Kaufman, M.D., Ph.D., Professor, Director of Cell Therapy Program, University of California, San Diego

NK cells can be routinely produced from human pluripotent stem cells – both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). hESC/iPSCs-derived NK cells have phenotype and function similar to peripheral blood NK cells and can be expanded into clinical-stage doses. hESC/iPSC-derived NK cells serve as a platform to test novel NK cell-specific CARs with improved anti-tumor activity.

12:20 pm Sponsored Presentation (Opportunity Available)

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

1:05 Session Break

AT THE INTERFACE OF INNATE AND ADAPTIVE IMMUNITY

2:05 Chairperson's Opening Remarks

Holger Lode, Ph.D., Professor and Chair of Pediatrics, Pediatric Hematology and Oncology, University Medicine Greifswald

2:10 Role & Exploitation of Invariant NKT Cells in Anti-Tumor Immune Responses

Mark ExleyMark Exley, Ph.D., Vice President, Agenus

We functionally defined two distinct human CD1d-reactive ‘NKT’ populations, invariant and ‘non-invariant’, from blood and tissues. NKT cells produce high levels of various cytokines/chemokines and potent CD1d-specfic cytotoxicity. NKT have physiological roles in anti-tumor and anti-viral responses. Reversible defects of NKT from cancer and other patients have led to promising translational observations. Our anti-NKT mAb is in clinical trials ex vivo, has been humanized and used in vivo, and is widely used in research. NKT can positively or negatively regulate anti-tumor immunity via NK and dendritic cells (DC). In mice, we found that interactions between NKT and CD1d+ DC augment Th1-type anti-viral and anti-tumor immunity – promising for therapy directly and with DC-based and other vaccines. NKT from tumor-bearing mice had reversible defects, similar to those we first identified in cancer patients. In humans, NKT cells appear to contribute to protective responses against cancers and viruses, and cancer patient survival is associated with Th1-biassed NKT. We describe our iNKT clinical trial in advanced melanoma. Further iNKT augmentation is in progress.

 2:55 Innate Immunotherapy of Cancer and a Crossroad to Checkpoint Blockade

Holger LodeHolger Lode, Ph.D., Professor and Chair of Pediatrics, Pediatric Hematology and Oncology, University Medicine Greifswald

We demonstrate by genotype and functional parameters that the mechanism of action is induction of antigen specific Ab-dependent cellular cytotoxicity (ADCC) in treated patients. Importantly, we describe for the first time that ADCC at sub-therapeutic drug concentration levels upregulates the inhibitory checkpoint PD-1/PD-L1 on tumor and effector cells. Combination of dinutuximab beta Apeiron with PD-1/PD-L1 blockade (nivolumab) results in synergistic treatment effects in vitro and in vivo.

3:40 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Problem Solving Roundtable Discussion

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

5:15 Welcome Reception in the Exhibit Hall with Poster Viewing

WEDNESDAY, December 6

8:00 am Morning Coffee

TARGETING MYELOID CELLS IN THE TUMOR MICROENVIRONMENT

8:40 Chairperson's Opening Remarks

Jeremy R. Graff, Ph.D., CSO and Senior Vice President, Research, Biothera Pharmaceuticals, Inc.

8:45 Imprime PGG - A Yeast-Derived Pathogen-Associated Molecular Pattern (PAMP) Triggers the Anti-Cancer Immunity Cycle to Potentiate the Efficacy of Immune Checkpoint Inhibitors

Jeremy GraffJeremy R. Graff, Ph.D., CSO and Senior Vice President, Research, Biothera Pharmaceuticals, Inc.

Imprime has been safely administered to >400 human subjects. Imprime triggers a cascade of immune activating events that re-polarize the immunosuppressive tumor microenvironment and elicit maturation of antigen presenting cells. Unlike other PAMPs (TLR and STING agonists), Imprime is administered systemically. In preclinical tumor models, Imprime robustly enhances the anti-tumor efficacy of CPIs. Accordingly, Imprime is now being explored in multiple Phase II clinical trials in combination with pembrolizumab.

9:15 Potent Anti-Tumor Immunity Is Induced by STING Activation in the Tumor Microenvironment Using a Synthetic Human STING-Activating Cyclic Dinucleotide

Kelsey GauthierKelsey Gauthier, Ph.D., Scientist, Aduro BioTech

I will describe how a novel synthetic CDN derivative (ADU-S100) that has improved STING-activating and anti-tumor properties as compared to naturally derived CDNs was developed for clinical translation. I will show that activation of STING through IT administration of ADU-S100 results in effective anti-tumor efficacy and survival in several mouse syngeneic tumor models. I will discuss some of the mechanisms by which ADU-S100 induces tumor regression and plans for a Phase I clinical study with ADU-S100 to evaluate the safety and tolerability and possible anti-tumor effects in subjects with cutaneously accessible malignancies.

9:45 Targeting Metabolic Vulnerabilities of MDSCs to Enhance the Anti-Tumor Activity of PD-1 Blockade

Bin ZhengBin Zheng, Ph.D., Assistant Professor, Dermatology, Harvard Medical School, Massachusetts General Hospital

Our findings demonstrate a selective, inhibitory effect of phenformin, a mitochondrial complex 1 inhibitor, on G-MDSCs-driven immune suppression and support that phenformin improves the anti-tumor activity of PD-1 blockade immunotherapy in melanoma.

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

 

DENDRITIC CELL-BASED IMMUNOTHERAPIES

10:45 Allogeneic DC-Based Immunotherapies

Alex Karlsson-ParraAlex Karlsson-Parra, M.D., Ph.D., CSO, Immunicum

Immunicum’s lead development candidate INTUVAX® uses dendritic cells harvested from healthy human donors that are specifically activated to produce significant amounts of vigorous immune stimulatory factors. By administration through intratumoral injection, these cells induce a local inflammatory reaction, leading to a local destruction of tumor cells and recruitment of the patient’s own dendritic cells into the tumor environment.

11:30 Development of Pluripotent Stem Cell-Based Therapies for Neurologic and Oncologic Disorders

Katharine Spink, Ph.D., Executive Vice President and COO, Asterias Biotherapeutics

Our group has established protocols to produce oligodendrocyte progenitors that upon transplantation into animals with spinal cord injuries can remyelinate denuded axons, induce axonal sprouting, and improve locomotor activity. Extensive preclinical studies have been completed to examine the activity, biodistribution, dosing, delivery, and potential toxicity and tumorigenicity of the oligodendrocyte progenitors. In collaboration with Cancer Research UK, Asterias is preparing for a clinical trial using these hESC derived dendritic cells as a cancer immunotherapy in non-small cell lung carcinoma in the neoadjuvant setting.

12:15 A Novel Phenotypic Approach for Predicting Tumor Response

Mark_ParisMark Paris, Ph.D., Associate Director, Translational Applications, Mitra Biotech

Mitra Biotech has developed and clinically validated our fully human ex-vivo platform technology (CANscript™)
. CANscript ™ uses patient material (tumor, autologous ligands and PBMC) to explore the mechanism of action and predict efficacy for clinically-directed compounds in a modality-agnostic way using phenotypic effects.
 This talk will explore the effects of anti-PD1 on CANscript tumor culture as insight into the capabilities of the platform.

12:45 Dessert Break in the Exhibit Hall with Poster Viewing


1:15 PLENARY KEYNOTE SESSION Click here for more information
Manufacturing Chimeric Antigen Receptor T Cells for Early Phase Clinical Trials
David F. Stroncek, M.D., Chief, Cell Therapy Section, Transfusion Medicine, NIH Clinical Center
Evolution of Cancer Immunotherapy
Ramy Ibrahim, M.D., VP, Clinical Development, Parker Institute for Cancer Immunotherapy

2:50 Close of Targeting Innate Immune Cells