Cambridge Healthtech Institute’s Inaugural

Targeting Innate Immunity

Differentiating Friends from Foes

September 24 - 25, 2019


As our knowledge of the complex innate immune system increases, new opportunities to develop novel treatments by utilizing the innate immune cells are significantly enhanced. Cambridge Healthtech Institute's Inaugural Targeting Innate Immunity Congress will convene all the thought leaders including industry experts, academic researchers and clinicians to deepen our understanding of the innate immunity and how to harness their power for effective immunotherapies. This 2-day congress focuses on the current landscape and novel advances in the field of innate immunotherapy such as natural killer cells, macrophages and dendritic cells. Be part of the conversation on mechanisms of action of innate cells, effective modulating strategies, the impact of tumor microenvironment and many more.

Final Agenda

TUESDAY, SEPTEMBER 24

8:00 am Welcome Remarks from Conference Director

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

8:10 Chairperson’s Opening Remarks

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


8:15 KEYNOTE PRESENTATION:

 

Beyond T Cell Immunotherapy

Shiladitya_SenguptaShiladitya Sengupta, PhD, Principle Investigator, Engineering in Medicine, Brigham and Women’s Hospital, Harvard Medical School and Massachusetts Institute of Technology

The talk shall address novel findings in the role of immune cells other than T cells in exerting an anticancer effect, especially novel immune checkpoints and engineering novel therapeutic approaches to activate these cells. We anticipate that a robust immune response that encompasses the different pillars of the immune system, together with T cells, is critical for improving the outcomes with immunotherapy.

ENGINEERING STRATEGIES FOR NK, NKT AND GAMMA DELTA T CELLS

8:45 Her2-CAR Engineered Natural Killer Cell Line as Off-the-Shelf Adoptive Immunotherapy in Solid Cancer

Tonn_TorstenTorsten Tonn, MD, PhD, Group Leader, Research Laboratory Experimental Transfusion Medicine; Professor, Transfusion Medicine, Medical Faculty Carl-Gustav-Carus, Technische Universität Dresden, Germany

This presentation will summarize preclinical data with CAR-NK cells in murine glioblastoma (GBM) models, and describe the ongoing clinical development of ErbB2/HER2-specific NK-92/5.28.z cells, a CAR-engineered derivative of the human NK cell line NK-92 currently applied in the CAR2BRAIN Phase I clinical trial (NCT03383978, clinicaltrials.gov) as an off-the-shelf cellular therapeutic for the treatment of relapsed glioblastoma.

9:15 Translation of Pluripotent Cell-Derived Engineered NK Cells as a Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy

Jode GoodridgeJode Goodridge, PhD, Senior Scientist, Cancer Immunotherapy, Fate Therapeutics

In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing.

9:45 Networking Coffee Break

10:05 Advances in Tri-Specific Killer Engager (TriKE) Molecules for NK Cell Antigen-Specific Recognition of Tumor Cells in High Risk MDS and Refractory AML Settings

Felices_MartinMartin Felices, PhD, Assistant Professor of Medicine, Co-Director, Translational Therapy Laboratory, Hematology, Oncology, and Transplantation, University of Minnesota

Tri-specific killer engager (TriKE) molecules drive NK cell antigen-specific recognition of tumor cells coupled with an expansion signal. These molecules, which essentially form a cytolytic bridge between NK cells and tumor cells, have been validated preclinically in a number of cancer settings and received FDA IND approval for a clinical trial in the high risk MDS and refractory AML setting.

10:35 Bispecific Gamma Delta T Cell Engagers for Cancer Immunotherapy

Hans-J-van-der-VLIETHans J. van der Vliet, Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, The Netherlands

We show that a novel bispecific nanobody-based construct targeting both Vg9Vd2-T cells and EGFR induced potent Vg9Vd2-T cell activation and subsequent tumor cell lysis both in vitro and in an in vivo mouse xenograft model. In combination with the conserved monomorphic nature of the Vg9Vd2-TCR and the facile replacement of the tumor-specific nanobody, this immunotherapeutic approach can be applied to a large group of cancer patients.

11:05 Novel Innate Killer Cell Platform for Empowering Cell Therapies for Cancers

Mark_ExleyMark A. Exley, PhD, Vice President, Cellular Immunology, AgenTus Therapeutics, Inc.

Translating the success of immune cell therapies in early solid tumor trials to wider use and broader durable responses requires dealing with several major hurdles, including practical logistics, prevention of relapse and control of serious side-effects. Allogeneic innate killer cell platforms offer potential to improve all these areas, alone and in combination with CARs and rTCRs. We will describe the status of our approaches exploiting innate killer cells in the context of the field, including clinical plans.

Celetrix 11:35 Accessing Innate Immunity Cells by Electroporation

Jian_ChenJian Chen, PhD, CEO, Celetrix Electroporation

Our ability to modify the innate immunity cells would enable designed and targeted therapies. Electroporation of NK cells, macrophages, dendritic cells has unique challenges due to their special biological and physical properties. A new electroporation technology is introduced to address the cell size transformation issue and has achieved significant improvements.

12:05 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:35 Session Break

THE ROLE OF ONCOLYTIC VIROTHERAPY IN IMMUNOTHERAPY

1:30 Chairperson’s Remarks

Fukumura_DaiDai Fukumura, MD, PhD, Deputy Director of Edwin L. Steele Laboratory and Investigator, Massachusetts General Hospital; Associate Professor, Harvard Medical School


1:35 The Role of Natural Killer Cells in Cancer Immunotherapy and Oncolytic Virotherapy

Yu_jianhuaJianhua Yu, PhD, Professor, Hematology & Hematopoietic Cell Transplantation, City of Hope

We discovered that innate immune cells can limit the efficacy of virotherapy at the early treatment stage due to their eradication of virally-infected GBM cells, limiting oHSV propagation. On the other hand, the oncolytic virus treatment combines the effects of both virotherapy and immunotherapy. Our recent work shows promising to modulate innate immune cells and increase oHSV viral spread in the solid tumor and thereby enhances the efficacy of oncolytic virotherapy.

2:05 ONCR-177, an Oncolytic HSV-1 Designed to Potentiate Systemic Anti-Tumor Immunity

Feau_SoniaSonia Feau, PhD, Associate Director, Immunology, Oncorus

ONCR-177 is a highly modified recombinant oncolytic herpes simplex virus (oHSV) designed for the treatment of solid tumor indications. ONCR-177 is proposed to have a dual mechanism of action whereby the microRNA attenuation strategy allows for selective oncolysis of tumors cells and the transgenes mediate potent stimulation of systemic anti-tumor immunity. This talk will explain how this modality combined with immunologic payloads can enhance innate and adaptive immune responses in the tumor microenvironment.

MACS-MiltenyiBiotec 2:35 Tools to Advance Translational CAR NK Research

Mahlios_JoshJosh Mahlios, PhD, Senior Product Manager, Miltenyi Biotec

Today, the possibility of implementing new therapeutic approaches using expanded and genetically modified NK cells presents exciting therapeutic opportunities, along with unique experimental challenges.  Aside from reliably sourcing and isolating these cell populations, significant obstacles exist for researchers when it comes to the efficient and reproducible activation, transduction, and expansion of NK cells for therapeutic purposes. Discover the tools that enable CAR NK cell manufacturing, from basic research to clinical settings using MACS technology.

3:05 Refreshment Break with Exhibit and Poster Viewing

REPROGRAMMING TUMOR MICROENVIRONMENT: TARGETING MYELOID CELLS, DENDRITIC CELLS AND INNATE LYMPHOID CELLS

3:45 Chairperson’s Remarks

weiskopf_kippKipp Weiskopf, MD, PhD, Resident Physician, Internal Medicine, Brigham and Women’s Hospital


3:45 Reprogramming Immune Cells in the Tumor Microenvironment to Treat Pancreatic Cancer

Gerber_ScottScott A. Gerber, PhD, Assistant Professor, Co-Director, Center for Tumor Immunology Research, Surgery, Microbiology, Immunology, Radiation Oncology, University of Rochester Medical Center

We have devised a therapy that targets both adaptive and innate intratumoral cells, and when combined with stereotactic body radiotherapy, results in complete cures in an orthotopic model of pancreatic cancer. Furthermore, our therapy, although given locally, stimulates a systemic anti-tumor immune response capable of eliminating distal metastases. This two-pronged approach is critical for optimal therapeutic response.

4:15 Receptor Mediated Antigen Delivery and Simultaneous Metabolic Modulation of Dendritic Cells for Inducing Tumor Immunity

Hegde_SubramanyaSubramanya Hegde, PhD, Senior Scientist III, Foundational Immunology, Abbvie

Dendritic cells (DCs) play a major role in both inflammatory diseases and cancer. DCs within the tumor are inefficient in taking up, processing and presenting the tumor antigens effectively. Reprogramming DC metabolism and targeting the tumor antigens via surface receptors could improve anti-tumor immune response.

4:45 Innate Lymphoid Cell (ILC) Functional Manipulation for Innovative Cancer Immunotherapy

Trabanelli_SaraSara Trabanelli, PhD, Research Associate, Oncology, Ludwig Institute for Cancer Research, University of Lausanne, Switzerland

We have recently reported the identification of novel, dominant ILC2-dependent circuits of immunosuppression in cancer patients. ILC2 may therefore represent attractive cell targets to reprogram the immunosuppressive tumor microenvironment. By decoding the transcriptional programs of human ILC2 we have identified candidate targets for ILC2 functional reprogramming. By therapeutically interfering with these circuits we are exploring the impact of these discoveries in preclinical mouse models, in view of Phase I clinical trials.

Sino-Biological 5:15 Comprehensive Bioreagent and CRO Services

Burgess_RobRob Burgess, PhD, Chief Business Officer, Sino Biological, Inc.

Founded in 2007, Sino Biological, Inc. is a global leader in the development and manufacturing of affordable, high-quality ISO9001-certified reagents, including, but not limited to, recombinant proteins, antibodies and cDNA clones—all in-house. The company boasts the world’s largest selection of recombinant proteins at 6000+, and acts as a one-stop shop for researchers and pharmaceutical companies around the world.  We help our customers to obtain the best reagents and services to accelerate the pace of research and drug discovery to improve human health.  An overview of the company’s product and CRO service portfolios will be given.

5:30 Welcome Reception with Exhibit and Poster Viewing

6:30 End of Day

WEDNESDAY, SEPTEMBER 25

8:00 am Breakfast Breakout Roundtable Discussions

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. View details on the topics and moderators here

Table 1: From Bench to Bedside to Industry

Moderator: Colleen Delaney, MD, MSc, Founder and CSO, Executive Vice President, Research and Development, Nohla Therapeutics

 

Table 2: Clinical Development of CAR – NK Cells – Challenges and Opportunities

NEW Moderator: Rizwan Romee, MD, Associate Professor of Medicine, Haploidentical Donor Transplant Program, Oncology/BMT and Leukemia Program, Dana Farber Cancer Institute, Harvard Medical School

 

Table 3: Targeting Dendritic Cells to Enhance T Cells Responses in Cancer

Moderator: Sonia Feau, PhD, Associate Director, Immunology, Oncorus


8:55 Chairperson’s Remarks

Mark_ExleyMark A. Exley, PhD, Vice President, Cellular Immunology, AgenTus Therapeutics, Inc.


9:00 KEYNOTE PRESENTATION: Case Studies in Cellular Therapy: Perspective from Three Regulatory Agencies

Callahan_MichaelMichael V. Callahan MD, DTM&H, MSPH, Director, Clinical Translation, Vaccine & Immunotherapy Center (VIC), Massachusetts General Hospital, Harvard Medical School; President & Chief Medical Officer, United Therapeutics Corporation

In recent years there has been a dramatic increase in regulatory filings for allogenic cellular therapies across three regulatory agencies: the U.S. Food and Drug Administration, Health Canada and the National Medical Products Administration (NMPA; formerly Chinese FDA). Increased clinical experience in East and West have identified promising cell therapy candidates that meet the demand for safe, immediate use, and more cost-viable cell therapies while also raising vigilance about cell therapies associated with severe adverse events. Improved safety characteristics and clinical experience managing adverse events results have prompted increased filings for safer, commercially viable next-generation natural killer cell, mesenchymal stem cell and γδ T cells. This presentation will review common features in pre-clinical package development that hinder entry into clinic and discuss common adverse events for recent cell therapy trials in three nations. 

MODULATING MACROPHAGES IN THE TUMOR MICROENVIRONMENT

9:30 FEATURED PRESENTATION: CAR Macrophage Immunotherapy: A New Frontier for Innate Immunity

Klichinsky_MichaelMichael Klichinsky, PharmD, PhD, Co-Founder, Vice President, Discovery, Carisma Therapeutics

Our approach can overcome the hurdles of cell therapy in the treatment of solid tumors by modulating the tumor microenvironment (TME) through macrophages with key characteristics: recruitment and access to the solid tumor TME, ability to survive in the hostile solid tumor milieu, maintenance of an anti-tumor phenotype in the presence of immunosuppressive factors, capacity to selectively destroy cancer cells, and activation of an adaptive immune response by presenting engulfed tumor material.

Medicenna 10:00 Tipping the Balance Towards Success in a Phase 2b Recurrent GBM Trial: Overcoming the Tumor and its Microenvironment by Targeting the IL4R Using MDNA55

Merchant FaharFahar Merchant, PhD, President, CEO, Medicenna Therapeutics

IL4R is up-regulated in GBM as well as in infiltrative myeloid derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) that make up to 40% of the tumor mass. MDNA55 is a novel IL4-targeted fusion toxin administered intratumorally via MRI-guided convection enhanced delivery as a single treatment for rGBM. In addition to a direct cytotoxic effect on IL4R-expressing tumor cells, MDNA55 could have additional therapeutic effects through elimination of IL4R-expressing MDSCs and TAMs in the glioma microenvironment, alleviating the immune block associated with cancer. The role of IL4R expression on survival outcomes and therapeutic benefit from the Phase 2b clinical trial of MDNA55 in one of the most aggressive tumor types will be presented.

10:30 Coffee Break with Exhibit and Poster Viewing

11:10 Modulating Macrophage Activities for Disease Intervention

Jianzhu_Chen Jianzhu Chen, PhD, Professor of Biology, Biology & Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

We have screened macrophage responses to over 4,000 compounds, including FDA-approved drugs, bioactive compounds and natural products, and identified compounds that can polarize macrophages from M1 to M2 or vice versa. We have validated selected compounds to drive tumor-associated macrophages to inflammatory phenotype in vivo to achieve anti-tumor effect alone or in combination with antibody therapeutics. These studies elucidate molecular basis underlying macrophage heterogeneity and provide a basis for modulating macrophage activities for disease intervention.

11:40 Myeloid Derived Suppressor Cell (MDSC): The Queen Bee of the Tumor Microenvironment (TME)

Tesi_RJ RJ Tesi, MD, CEO, CMO, INmune Bio

The most efficient way to reverse TME immunobiology is to target myeloid derived suppressor cells (MDSC). This talk will address the complexity of the TME and how it contributes to failure of therapy, understanding of how targeting soluble TNF offers a solution to the resistance to therapy when part of combination therapy; and results of the Phase I trial of INB03 in patients with advanced cancer.

12:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:40 Session Break

ADVANCING INNATE CELL THERAPIES TO THE CLINIC

1:40 Chairperson’s Remarks

Romee_Rizwan Rizwan Romee, MD, Associate Professor of Medicine, Haploidentical Donor Transplant Program, Oncology/BMT and Leukemia Program, Dana Farber Cancer Institute, Harvard Medical School


1:45 What do Tumor Cells do to NK Cells? - Harnessing the Tumor-NK Interaction for Clinical Benefit

Mark Lowell Mark Lowdell, PhD, Director, Centre for Cell, Gene & Tissue Therapeutics, RFH; Professor, Cell & Tissue Therapy, University College London


2:15 Targeting TIM-3 and IL-1b in Cancer Immunotherapy: Deciphering Key Roles in the TME

Jayaraman_Pushpa Pushpa Jayaraman, PhD, Senior Investigator I, Exploratory Immuno Oncology, Novartis Institutes for Biomedical Research

The success of PD-1 pathway inhibitors has led to the rapid expansion of clinical trials in immuno-oncology, including multiple trials exploring partner pathways to enhance responses and durability and to tackle nodes of resistance. Next-generation inhibitors including TIM-3 and IL-1b modulate innate immune biology, and preclinical research reveals novel and critical mechanisms of action for these pathways. Translational data from clinical trials also informs understanding of novel mechanisms. Our work highlights the pathophysiological role of TIM-3 and IL-1b in tumor immunomodulation and inhibitory consequences on T cell function and checkpoint blockade in cancer.

2:45 Off-the-Shelf NK Cells for Malignancies and Infections

Vasu__Sumithira Sumithira Vasu, MBBS, Assistant Professor, The Ohio State University Medical Center

Natural killer cells have shown efficacy in hematologic malignancies and some solid tumors. Administering NK cell therapy without cytokines requires an ex vivo expanded, readily available off-the-shelf NK product. We discuss a framework of evaluating these third-party NK cells in clinical trials.

3:15 Refreshment Break with Exhibit and Poster Viewing

3:45 Tumor Cell-Autonomous Mechanisms Regulating Activity of NK Cells

Mitsiades_Constantine Constantine Mitsiades, MD, PhD, Assistant Professor, Medicine, Harvard Medical School; Principal Investigator, Medical Oncology, Dana-Farber Cancer Institute

Despite extensive efforts towards developing diverse NK cell-based therapeutic approaches against human neoplasias, the mechanisms which operate in tumor cells to regulate the degree of their responsiveness vs. resistance to NK cells remain incompletely understood.  This presentation will provide an overview of recent developments in the characterization of cell-autonomous mechanisms which enhance or suppress the response of malignant cells to NK cells and discuss the implications of these developments on current and future efforts to develop NK cell-based immunotherapies.

4:15 Off-the-Shelf, Engineered NK Cell Lines for Patient-Specific Cancer Treatment

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

We have developed the NK cell line NK-92 into an “off-the-shelf” activated NK (aNK) cell therapeutics. The safety of aNK as well as their activity against a broad range of cancers have been confirmed in Phase I trials in the U.S., Canada and Europe. aNK cells can be administered in the outpatient setting and serve as a universal cell-based therapy without need for individualized patient matching. aNK cells have been bioengineered to incorporate a high-antibody binding Fc-receptor (haNK). Both aNK and haNK cells can be equipped with chimeric antigen receptors (CARs) (taNK and t-haNK) to further optimize targeting and potency in the therapeutic setting.

4:45 The Role of Off-the-Shelf Expanded Hematopoietic Progenitors as Adoptive Therapy to Improve Treatment Outcomes in AML Patients

Delaney_Colleen Colleen Delaney, MD, MSc, Founder and CSO, Executive Vice President, Research and Development, Nohla Therapeutics

This talk will focus on the use of cellular therapies in the setting of AML treatment, and potential mechanisms of action in inducing an autologous anti-tumor immune response.

5:15 End of Congress

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