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:

Therapeutic Targeting of Trained Immunity

Netea_MihaiMihai G. Netea, PhD, Professor, Internal Medicine, Radboud University Medical Center, The Netherlands

I will share my thoughts and vision of how to target innate immune cells and regulate trained immunity to achieve long-term therapeutic benefits in a range of immune-related diseases. These include conditions characterized by excessive trained immunity, such as inflammatory and autoimmune disorders, allergies and cardiovascular disease and conditions driven by defective trained immunity, such as cancer and certain infections.

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

Valamehr_BobBob Valamehr, PhD, MBA, Chief Development Officer, Fate Therapeutics, Inc.

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.

11:35 Sponsored Presentation (Opportunity Available)

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.

2:35 Sponsored Presentation (Opportunity Available)

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

Jandus_Camilla]Camilla Jandus, MD, PhD, Principal Investigator, Assistant Professor, Oncology, 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.

5:15 Welcome Reception with Exhibit and Poster Viewing

6:15 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

MODULATING MACROPHAGES IN THE TUMOR MICROENVIRONMENT

8:55 Chairperson’s Remarks

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


9:00 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.

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.

10:00 Sponsored Presentation (Opportunity Available)

10:30 Coffee Break with Exhibit and Poster Viewing

11:10 Modulating Macrophage Activities for Disease Intervention

Jianzhu_ChenJianzhu 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_RJRJ 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 pm Sponsored Presentation (Opportunity Available)

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

1:10 Session Break

ADVANCING INNATE CELL THERAPIES TO THE CLINIC

2:10 Chairperson’s Remarks

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


2:15 Contribution to Angiogenesis from Innate Immunity: The Role of Natural Killer Cells within the Tumor Microenvironment

Albini_adrianaAdriana Albini, PhD, Professor of General Pathology, Medicine and Surgery, University Milan Bicocca, Italy

We reported that tumor infiltrating NK cells (TINKs) in non-small cell lung cancer, are enriched in the pro-angiogenic-decidual-like CD56brightCD16- NK cell subset, able to produce large amounts of VEGF, PlGF and IL-8 ex vivo, thus activating endothelial cell chemotaxis and tube formation. Interestingly this angiogenic switch is mediated by TGFβ, largely produced by tumors and tumor microenvironment. Our findings strongly suggest a pro-angiogenic role of CRC-derived NKs as well as NKs derived from PE of patients with mesothelioma and lung carcinoma.

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

Vasu__SumithiraSumithira 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 Memory-Like NK Cells for Relapsed Myeloid Malignancies

Romee_RizwanRizwan Romee, MD, Associate Professor of Medicine, 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.

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

Klingemann_HansHans 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_ColleenColleen 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

Japan-Flag   Korea-Flag   China-Simplified-Flag   China-Traditional-Flag