Cambridge Healthtech Institute’s Inaugural

Cancer Immunotherapy

Emerging Biology, Targets and Strategies

March 7 – 9, 2016 | Moscone North Convention Center | San Francisco, CA
Part of the 23rd International Molecular Medicine Tri-Conference

 

Cancer immunotherapy, hailed as the biggest breakthrough in modern cancer treatment, has quickly permeated mainstream basic and clinical research. With vast excitement seen over the past few years stirred by remarkable clinical efficacy of immunotherapy agents, the emergence and rapid growth of biotechs and pharmaceutical partnering, and recent regulatory approvals, it has become clear that immuno-oncology research and the development of immunotherapies and their combinations will continue to revolutionize cancer treatment. 

Cambridge Healthtech Institute’s inaugural Cancer Immunotherapy meeting 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; discuss advances in adoptive cell therapies and combinations, as well as to provide updates on clinical findings.

Final Agenda

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Monday, March 7

10:30 am Conference Program Registration Open


HARNESSING NK CELLS FOR NEW ADOPTIVE CELL THERAPIES

11:50 Chairperson’s Opening Remarks

James Smothers, Ph.D., Senior Director and Head, Discovery, Immuno-Oncology & Combinations DPU, GlaxoSmithKline


»» 12:00 PM KEYNOTE PRESENTATION: Enhancing NK Cell Function for Transplantation and Cancer Therapy

Jeffrey Miller, M.D., Professor, Medicine; Deputy Director; Roger L. and Lynn C. Headrick Chair in Cancer Therapeutics, University of Minnesota Cancer Center

We have performed a number of clinical trials using autologous and allogeneic NK cells. IL-15, a natural cytokine that is critical for NK cell development and homeostasis will be discussed. I will discuss NK cell receptor immunogenetics and their importance in predicting transplantation outcomes. We have discovered a new subset of NK cells termed adaptive with properties of immunologic memory induced by cytomegalovirus. Lastly, I will review how NK cells can be targeted to tumors by bi-specific and trispecific killer engagers and discuss the future of targeted NK cell therapeutics.


12:30 Immunosurveillance and Immunotherapy of Cancer-Mediated by Natural Killer Cells

David H. Raulet, Ph.D., C.H. Li Professor of Immunology and Pathogenesis; Co-Chair, Department of Molecular and Cell Biology, University of California, Berkley

We provide evidence that natural killer cells, and receptors they express that recognize cancer cells, provide protection against cancers arising in spontaneous mouse models of cancer. Furthermore, we develop evidence that NK cell activity is often suppressed in tumors by several mechanisms. We successfully tested several approaches to prevent the inactivation of NK cells within tumors, and show evidence for therapeutic benefit in preclinical models.

1:00 Session Break

Charles River Discovery1:15 Luncheon Presentation I: Combination Immune Checkpoint Inhibitors for the Treatment of Colon Carcinoma in Humanized NSG Mice.

Martin R. Graf, Ph.D., Associate Director, Research, Operations, Charles River Laboratories

The therapeutic efficacy of combined anti-CTLA4 and anti-PD1 was evaluated in the human RKO colon carcinoma model using HLA-A matched CD34+-NSG humanized mice. Mice with established RKO tumors were treated with ipilimumab and pembrolizumab (100g each) on days 1, 4, 9, 12 and 15 of the study. Treatment with the combined immune checkpoint inhibitors significantly reduced tumor progression (p<0.001) as compared to control CD34+-NSG mice that were treated with non-specific IgG.

Thomson Reuters logo1:45 Luncheon Presentation II: Knowledge Based Approaches to New Targets in Cancer Immunotherapy

Richard Harrison, CSO, Product Management, Thomson Reuters

We are applying knowledge based approaches to scout biological pathways for potential new targets for immune based therapies for cancer. This presentation will focus on an overview of the field of cancer immunotherapy, a review of new initiatives, and a look at how these knowledge based approaches are being used to find potential new therapies for cancer treatment.

2:15 Session Break


CLINICAL TRIALS AND COMBINATIONS OF NK CELL THERAPY

2:30 Chairperson’s Remarks

James Smothers, Ph.D., Senior Director and Head, Discovery, Immuno-Oncology & Combinations DPU, GlaxoSmithKline

2:40 Cord Blood-Derived Natural Killer Cells for Treatment of Multiple Myeloma

Nina D. Shah, M.D., Medical Director & Assistant Professor, Stem Cell Transplantation Center, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

NK cells are ideal candidates for allogeneic cellular therapy, as they are safe and do not produce GVHD. We have developed a novel technique for large scale expansion of NK cells from cryopreserved cord blood (CB) units. In this presentation we will discuss the techniques of CB-NK expansion, the activity of these cells and our experience in a first-in-human trial for patients with multiple myeloma. We will also discuss possible mechanisms of action and future applications of this therapy not only for myeloma but a host of hematologic malignancies.

3:10 Utilizing Function-Enabled NK Cells for Cancer Immunotherapy

Todd A. Fehniger, M.D., Ph.D., Associate Professor, Department of Medicine, Oncology Division, Bone Marrow Transplantation & Leukemia Section, Washington University School of Medicine

Recent discoveries have revealed that NK cells remember prior activation, and our work defining and translating cytokine-induced memory-like NK cells from bench to the leukemia patient bedside will be discussed. In addition, we will review the basic science defining the importance of cytokine receptors for NK cell sustenance in vivo, and present recent translational results whereby monoclonal antibodies are combined with ‘next-generation’ function-enhancing cytokines for the immunotherapy of lymphoma.

3:40 Enhancing Antibody-Directed Innate Immunity to Improve Cancer Outcome

Paul M. Sondel, M.D., Ph.D., Reed and Carolee Walker Professor of Pediatrics and Human Oncology; Head, Division of Pediatric Hematology, Oncology and BMT; University of Wisconsin

We have used tumor-reactive mAbs combined with or linked to IL2 (immunocytokines) as an initial platform to induce NK-mediated innate anti-tumor effects in the lab and clinic. Combining this innate approach with radiation therapy and immunomodulatory immunotherapy is enabling engagement of adaptive immunity in tumor-bearing mice, with resultant tumor-specific memory. Our goal is to identify and refine combinations of “off the shelf” immunotherapies that can eliminate cancer.

Cellecta4:10 Driver-Map: Molecular Deconstruction of the Tumor Microenvironment

Gus Frangou, Ph.D., Director,Clinical Operations,Cellecta

Molecular profiles of the tumor microenvironment (TME) hold considerable promise for biomarker discovery. The talk describes a novel multiplex RNA-Tag-Seq pipeline to quantitatively assess the digital transcription profile of the TME and model tumor purity and infer the presence of infiltrating stromal/immune cells in clinical samples.

 

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session 

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

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Tuesday, March 8

7:00 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session 

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing


ADVANCES IN ADOPTIVE T-CELL THERAPY

10:05 Chairperson’s Remarks

Aidan Synnott, Ph.D., Oncology Discovery Site Director and Global Business Operations Lead, Charles River Laboratories

10:15 CAR T-Cells as Immunotherapy: Where Are We Now?

Marco Ruella, M.D., Clinical Fellow, Center for Cellular Immunotherapies (CCI), Perelman School of Medicine, University of Pennsylvania

Genetically-modified T-cells with chimeric antigen receptors (CARs) have been granted Breakthrough Therapy designation by the FDA at multiple institutions. Despite having been developed in the academic setting, many T-cell therapies are now entering an industry setting to be developed into commercial therapies to treat cancer. We will discuss the components of chimeric antigen receptors, the technologies used in making a T-cell product, some of the factors considered to be important for efficacy, and recent results in hematologic malignancies and solid tumors.

10:45 The ImmTAC Technology: A Cutting Edge Immunotherapy for Cancer Treatment

Martina Canestraro, Ph.D., Research Scientist, Preclinical Biology, Immunocore Limited

ImmTACs are bi-specific molecules formed from an affinity enhanced monoclonal T-cell receptor linked to an anti-CD3 specific antibody fragment (CD3-scFv). The mTCR recognises intracellular antigens that have been processed and displayed on class I MHC molecules; the CD3-scFv is a powerful effector function that redirects CD3+ T-cell activity to the tumour cells. Through the targeting of peptides presented by Class I HLA the ImmTAC has access to intracellular antigens that traditional antibody therapeutics are unable to target thus allowing the ImmTACs to recognise a greater variety of targets.

11:15 PANEL DISCUSSION: Current Challenges and Opportunities for CAR T-Cell Therapy

Moderator: James Smothers, Ph.D., Senior Director & Head, Discovery, Immuno-Oncology & Combinations DPU, GlaxoSmithKline

T-cells that have been genetically modified and redirected with a chimeric antigen receptor, or CAR, have shown unprecedented efficacy in B-cell malignancies. This panel discussion will tackle current challenges and emerging opportunities within this rapidly emerging space. Topics will include, but are not limited to:

  • Novel and emerging antigens for targeting
  • Challenges and opportunities in targeting solid tumors
  • Approaches for avoiding or controlling cytokine syndrome
  • Enhancing expansion and persistence of T-cells
  • Combination strategies to combat tumor microenvironment

Panelists:

David M. Spencer, Ph.D., CSO, Bellicum Pharmaceuticals, Inc.

Richard Morgan, Ph.D., Vice President, Immunotherapy, bluebird bio

Philippe Duchateau, Ph.D., CSO, Cellectis

Marco Ruella, M.D., Clinical Fellow, Center for Cellular Immunotherapies (CCI), Perelman School of Medicine, University of Pennsylvania

12:15 pm Session Break

12:25 Luncheon Presentation I: From Syngeneic to Humanized Mouse Models: Tools to Address Novel Cancer Immunotherapies

Jean-François Mirjolet, Technology Director, Oncodesign

Therapies such as CTLA-4 or PD-1 targeting antibodies have now received approval and others are under clinical evaluation. However, there is still a huge need in refining preclinical models to address efficacy but also to identify biomarkers. To answer these questions, case studies using syngeneic mouse models and tumor bearing humanized mouse will be described.

CellularTechnologyLtd_CTL12:55 Luncheon Presentation II: Multi Parametric Immune Monitoring Using Fluorescence-based, High Throughput Cell Imaging

Srividya Sundararaman, Ph.D., Staff Scientist, Research & Development, Cellular Technology Limited

CTL has developed a comprehensive Immune Monitoring platform for primary and secondary immune response to antigens; i.e. NK cytotoxicity, measurements of the magnitude and lineage of antigen induced T cells, cytotoxic ability of the cells, and antibody secreting B cells.

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing


EMERGING STRATEGIES FOR CHECKPOINT INHIBITOR COMBINATION IMMUNOTHERAPY

2:00 Chairperson’s Remarks

Jeff T. Hutchins, Ph.D., Vice President, Preclinical Research, Peregrine Pharmaceuticals

2:10 Featured Presentation: Big Wins for Small Molecules & Combinations in Immuno-Oncology

James Smothers, Ph.D., Senior Director & Head, Discovery, Immuno-Oncology & Combinations DPU, GlaxoSmithKline

Recent clinical success in immuno-oncology underscores the growing therapeutic value of monoclonal antibodies that block T-cell immune checkpoint pathways and engineered T-cells which directly target tumor antigens. In contrast, small molecule chemistry interventions have yet to evince such success in this growing area of medicines development despite this class of medicines having previously dominated oncology drug approvals. Despite this, a growing number of pre-clinical and clinical investigations are now poised to leverage novel value for small molecules in immune-oncology. Emerging strategies to combine tumor-targeting small molecule medicines with immuno-oncology therapies as well as opportunities to directly target immune modulation through small molecule chemistries will be discussed.

2:40 Blood-Based Biopsies in the Age of Immunotherapy: How Can We Use Circulating Stromal Cells?

Daniel Adams, Senior Research Scientist, Creatv MicroTech,Inc.

CellSieve™ filters isolate circulating stromal cells & circulating tumor cells disseminated from tumor masses allowing for tumor subtyping & stromal targeting. While providing sequential noninvasive sampling, analyzing multiple cell types enables a greater variety of information for immunotherapy treatment selection and monitoring treatment response.

ACEA Biosciences2:55 Label-Free Real-Time Monitoring of Immune Cell-Mediated Killing Using Cellular Impedance

Brandon Lamarche, Ph.D., Research Scientist, Research & Development, ACEA Biosciences, Inc.

Development of novel cancer immunotherapies requires killing assays capable of predicting long-term killing kinetics of immune cells in vivo. To address this unmet need, ACEA developed the label-free real-time xCELLigence assay to quantify immune cell killing kinetics. Case studies on NK/T cell-mediated cytolysis, ADCC, BiTE and CAR-T will be discussed.

3:25 Potent Anti-Tumor Immunity is Induced by STING Activation in the Tumor Microenvironment Using a Synthetic Human STING-Activating Cyclic Dinucleotide

Sarah McWhirter, Ph.D., Associate Director, STING Program, Aduro Biotech

Production of host type I interferon within the tumor microenvironment (TME), mediated by the Stimulator of Interferon Genes (STING) pathway, leads to priming of tumor-specific immunity. We hypothesized that direct activation of the STING pathway in the TME by intratumoral (IT) injection of STING-activating cyclic dinucleotides (CDNs) would be an effective therapeutic strategy to promote broad tumor-initiated T cell priming. 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 of ADU-S100 induces tumor regression and plans for a Phase 1 clinical study with ADU-S100 to evaluate the safety and tolerability and possible anti-tumor effects in subjects with cutaneously accessible malignancies.

3:55 Combination Immunotherapies – Opening the Gate: Increasing Tumor Infiltrating Activated T-Cells to Optimize and Expand the Benefits of Immune Checkpoint Therapies

Jeff T. Hutchins, Ph.D., Vice President, Preclinical Research, Peregrine Pharmaceuticals

PD-1 and CTLA-4-targeting drugs have significantly improved patient survival in both melanoma and NSCLC, although their efficacy has been limited to a minority of subjects. Phosphatidylserine (PS)-targeting antibodies have demonstrated the ability to override tumor immune suppression and reactivate immune responses when combined with immunotherapies, chemotherapies, radiation, and targeted treatments. Recent translational data demonstrate the potential of PS-targeting antibodies to mediate immune activation and improved anti-tumor responses in low PD-L1 tumor samples.

4:10 St. Patrick’s Day Celebration in the Exhibit Hall with Poster Viewing

 

5:00 Breakout Discussions in the Exhibit Hall

This interactive session provides attendees an opportunity to choose a specific discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Emerging Checkpoint Inhibitor Combinations

James Smothers, Ph.D., Senior Director and Head, Discovery, Immuno-Oncology & Combinations DPU, GlaxoSmithKline

  • What types of modalities/strategies are presenting combination opportunities with checkpoint inhibition?
  • Which are showing promise in the clinic?
  • What are novel pathways for targeting to obtain synergistic effects with checkpoint antibodies?
  • What predictive measures can we use to determine rational combinations?

Emerging Targets in Cancer Immunotherapy

Xingxing Zang, Ph.D., Associate Professor, Microbiology, Immunology and Medicine, Albert Einstein College of Medicine

  • Mechanisms by which co-stimulation and co-inhibition of B7 family and CD28 family regulate T cells
  • Novel checkpoint targets beyond CTLA-4 and the PD-1/PD-L1 pathway
  • Novel drug development

6:00 Close of Day

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Wednesday, March 9

7:00 am Registration Open

7:00 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Plenary Keynote Session Panel 

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall


AGONIST – PD-1 COMBINATION IMMUNOTHERAPY

10:50 Chairperson’s Remarks

Andrew D. Weinberg, Ph.D., Chief, Laboratory of Basic Immunology, Providence Cancer Center

11:00 Preclinical Evaluation of an Agonist Antibody Targeting ICOS

Robert Mabry, Ph.D., Director, Protein Sciences and Antibody Technology, Jounce Therapeutics

Jounce is developing an agonistic antibody to the co-stimulatory molecule ICOS. Preclinical studies demonstrate that anti-ICOS agonistic antibodies are efficacious in syngeneic tumor models, with enhanced efficacy observed in combination with PD-1 inhibition.

11:30 Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells

John C. Lin, M.D., Ph.D., Senior Vice President & CSO, Rinat, Pfizer

Immunotherapies targeting the programmed death 1 (PD-1) coinhibitory receptor have shown great promise for a subset of patients with cancer. However, robust and safe combination therapies are still needed to bring the benefit of cancer immunotherapy to broader patient populations. To search for an optimal strategy of combinatorial immunotherapy, we have compared the antitumor activity of the anti-4-1BB/anti-PD-1 combination with that of the anti-PD-1/anti-LAG-3 combination in the poorly immunogenic B16F10 melanoma model.

12:00 pm OX40 Agonist Combined with PD-1 and TGFb Receptor Blockade

Andrew D. Weinberg, Ph.D., Chief, Laboratory of Basic Immunology, Providence Cancer Center

Human OX40 agonists are currently being tested in the clinic and the rationale for this immunotherapeutic approach was based on their success in preclinical mouse tumor models. Our group has found that when OX40 agonists are delivered when the tumors are large in size the mice become resistant to their therapeutic effects. Therefore we tested two agents in combination with OX40 agonists in mice harboring large tumors: 1) PDL-1 blockade and 2) TGFb-receptor inhibitor. Both agents showed therapeutic synergy when combined with OX40 agonists and enhanced immune infiltration within tumors.

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing


NOVEL TARGETS FOR IMMUNOTHERAPY DEVELOPMENT AND SYNERGISTIC COMBINATIONS

1:50 Chairperson’s Remarks

Holbrook Kohrt, M.D., Ph.D., Assistant Professor, Medicine (Oncology), Stanford University Medical Center

2:00 Combination Immunotherapy to Enhance Efficacy of Tumor Targeting Antibodies

Holbrook Kohrt, M.D., Ph.D., Assistant Professor, Medicine (Oncology), Stanford University Medical Center

Recent studies indicate that the antitumor efficacy of therapeutic tumor-targeting antibodies can be augmented by the addition of agonistic antibodies targeting CD137. As ligation of CD137 provides a costimulatory signal in multiple immune cell subsets, combination therapy of CD137 antibody with therapeutic antibodies and/or vaccination has the potential to improve cancer treatment. Recently, clinical trials of combination therapies with agonistic anti-CD137 mAbs have been launched.

Sadly, we have learned that Dr. Holbrook Kohrt, a remarkable physician-scientist, lost his battle with hemophilia on February 24, 2016. We extend our sincere condolences to his family, friends, and the scientific community.


2:30 Emerging Targets in Cancer Immunotherapy: Beyond CTLA-4 and PD-1

Xingxing Zang, Ph.D., Associate Professor, Microbiology, Immunology and Medicine, Albert Einstein College of Medicine

CTLA-4 and the PD-1/PD-L1 pathway are current focuses in cancer immunotherapy. Dr. Zang will discuss other new immune checkpoints for future human cancer immunotherapy.

3:00 oxMIF as a New Therapeutic Target in Cancer

Michael Thiele, Ph.D., Manager, R&D, Research & Innovation, Baxalta Innovations GmbH

A newly discovered, disease-related isoform of the cytokine macrophage migration inhibitory factor (MIF), designated oxMIF, presents a potential target for novel therapies in cancers with a high unmet medical need. Unlike MIF, OxMIF is specifically expressed in cancerous tissue from patients with different solid tumors, but not in tissue with normal morphology or in healthy subjects. Human monoclonal antibodies (mAbs) directed against oxMIF demonstrated anticancer activity alone, and in combination with chemotherapeutic agents in mouse cancer models.

3:30 Potent Antitumor Activity of IL-2-Fc Fusion Proteins Through FcyR-Dependent Depletion of Regulatory T-Cells

Rodrigo Vazquez Lombardi, Post Graduate, Garvan Institute of Medical Research

 

4:00 Session Break


Immunomonitoring and Mechanism of Action of New Immunotherapies

4:10 Chairperson’s Remarks

Kip Harry, Director, Conferences, Cambridge Healthtech Institute

4:15 Imnunosequencing and Cancer

Catherine Sanders, Ph.D., Director, Scientific Liason, Adaptive Biotechnologies

Adaptive is at the forefront of immune-based discoveries, combining high-throughput sequencing and expert bioinformatics to profile T-cell and B-cell receptors. We bring the accuracy and sensitivity of our immunosequencing platform into laboratories around the world to drive groundbreaking research in cancer and other immune-mediated diseases. Adaptive also translates immunosequencing discoveries into clinical diagnostics and therapeutic development to improve patient care.

4:45 Biomarkers to Support the Development and Clinical Application of Immunotherapy Combinations

Jelveh Lameh, Ph.D., Executive Director & Head, BioPharma Services Laboratory, Genoptix Medical Laboratory, Inc., a Novartis Company

Biomarkers have successfully been applied to multiple aspects of cancer therapy. Up until now, biomarkers have been applied to various aspects of therapies that were targeted directly at the tumor cells. With the recent advances in immunotherapy, the rationale for combination therapies to circumvent resistance has emerged. Thus, application of biomarkers for such combination therapies is expected to improve patient outcomes.

5:15 Analytical Validation of Multiplex Assays on Simple-Plex Ella Platform for the Measurement of Cytokines

Teresa Davancaze, Principal Research Associate, Genentech

Immune check point inhibitors such as anti-PD-L1 have exhibited durable anti-tumor responses in a variety of cancer indications which break down the tolerogenic state of immune cells and activate T-lymphocytes. These activated lymphocytes release cytokines that directly stimulate immune effector cells at the tumor site and enhance cell recognition by cytotoxic effector cells for elimination of tumors. Measurement of cytokines is actively being pursued to study pharmacodynamic changes which can help understand the mechanism of action of immune checkpoint inhibitors. In this study, we show bioanalytical validation of cytokines assays in plasma on a novel multiplex platform, Simple-Plex Ella. Ella allows multiplexing of four analytes and consumes small sample volume of 25ul. Compared to conventional multiplex immunoassays such as Luminex, Ella offers the specificity of a single-plex ELISA since each sample is run in four channels, each specific to a unique analyte. The assays exhibited excellent sensitivity and specificity. The accuracy and precision were 80-120% and 10% respectively.

5:45 Close of Conference Program



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