- 腫瘤微環境 -
Our second Modulating the Tumour Microenvironment conference presents innovations for enhancing the immune anti-tumour response and overcoming inhibitory factors. It is becoming clear that many immunosuppressive mechanisms are at work. The checkpoint inhibitors are not living up to expectations, and for these and other antagonists to be effective, it is necessary to control Tregs and manipulate myeloid-derived and other suppressor cells in the tumour microenvironment (TME). The leaders in the field are also paying attention to the role of cytokines and the importance of Fc-engagement for effective targeting.

Final Agenda

Recommended Short Course*

SC2: The Tumour Microenvironment and Response to Cancer Immunotherapy - LEARN MORE

*Separate registration required.

11月18日(一)

12:00 Conference Registration (Foyer A)

THE KEY TO THERAPEUTIC SUCCESS
Auditorium VIII

13:30 Organiser’s Welcome

Nicole Lyscom, PhD, Senior Conference Director, Cambridge Healthtech Institute

13:35 Chairperson’s Opening Remarks

Dario Neri, PhD, Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich)

13:45 Using Antibodies to Target the Tumour Microenvironment - Good Intentions Can Often Lead to Unintended Consequences

Beers_StephenStephen Beers, PhD, Professor, Immunology and Immunotherapy, Centre for Cancer Immunology, Cancer Sciences Unit, University of Southampton

Despite the impact of monoclonal antibodies (mAb) in oncology, patient responses remain variable, therefore new mAb and strategies are required. Although the number of mAb reaching the clinic continues to rise, new targets are scarce and frequently fail. A key issue facing antibody drug development is understanding why promising candidates do not translate to clinical success. Here, we will show how mAb format can be critical to efficacy and how this could be particularly important when seeking to develop mAb to target the tumour microenvironment.

14:15 Fc-Dependent Expansion of Distinct Memory Populations Defines the Antitumor Efficacy of Checkpoint Immunotherapy

Sylvia Vincent, PhD, Scientist, Immuno-modulatory Drug Discovery, Agenus

We describe a novel mechanism by which distinct immune checkpoint antibodies require selective Fc-FcγR co-engagement between antigen-presenting cells (APCs) and T cells for the expansion of memory T cell subpopulations. We demonstrate that the Fc-dependent expansion of these memory populations is important for antitumor responses and is consistent between mice and man.

14:45 Targeted Cytokine Sweeping Activity Using New Bispecific Formats

Poul_Marie-AlixMarie-Alix Poul, PhD, Professor, Immunology, Biology-Life Science, University of Montpelier, IRCM

We have designed a new functional type of bispecific antibody combining binding to a tumor-specific recycling cell surface receptor and to soluble pro-tumoral factors. This bispecific format mediates the targeted sweeping of tumor-microenvironment soluble factors by the cancer cells themselves. Three bispecific antibody formats have been designed with 2, 3, or 4 antigen-binding sites and their sweeping efficiency and cancer cell growth inhibitory properties have been compared in cancer models.

15:15 Presentation to be Announced

 

15:30 Sponsored Presentation (Opportunity Available)

15:45 Networking Refreshment Break (Foyer D)


PLENARY KEYNOTE SESSION

16:15 Moderator’s Opening Remarks

Kerry Chester, PhD, Professor, Molecular Medicine, University College London Cancer InstituteKerry Chester, PhD, Professor, Molecular Medicine, University College London Cancer Institute

 

 

 

 

 

16:20 Bispecific, Soluble TCR as the Next Therapeutic Platform

Bahija Jallal, PhD, CEO and Director of the Board, ImmunocoreBahija Jallal, PhD, CEO and Director of the Board, Immunocore

Of the two adaptive immunity recognition motifs, only antibodies have been brought to patients. However, antibody therapeutics only recognize 10% of human proteome (surface-expressed). The other motif, T cell receptor (TCR), has potential to unlock 90% of the human proteome, but requires converting a low-affinity, specificity membrane receptor into a soluble therapeutic. IMCgp100, a soluble, TCR bispecific-targeting melanoma, is the most advanced soluble TCR therapeutic in development.

17:20 Attacking Cancer Cell Surfaceomes with Recombinant Antibodies

James A. Wells, PhD, Professor, Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California,
	San FranciscoJames A. Wells, PhD, Professor, Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California, San Francisco

The cell surface proteome (surfaceome) is the primary hub for cells to communicate with the outside world. Oncogenes are known to cause huge changes in cells and we find this translates to significant remodeling of the surfaceome. We generate recombinant antibodies to detect and then attack these cells by toxifying the antibodies or recruiting immune cells to kill. I’ll discuss the technologies for surface protein analysis, an industrialized platform for rapid antibody generation using phage display, and using these tool reagents for target validation.

Abcam 18:20 Welcome Reception in the Exhibit Hall with Poster Viewing (Rio Pavilion)

19:30 End of Day

 

11月19日(二)

07:45 Registration and Morning Coffee (Foyer A)

TARGETING IMMUNE CHECKPOINTS
Auditorium VIII

08:30 Chairperson’s Remarks

Stephen Beers, PhD, Professor, Immunology and Immunotherapy, Centre for Cancer Immunology, Cancer Sciences Unit, University of Southampton

08:35 Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy–Focus on FcγRII

Frendeus_BjoernBjörn Frendéus, PhD, CSO, BioInvent International AB

Immunotherapy with therapeutic antibodies has increased survival for patients with hematologic and solid cancers. Still, most patients fail to respond to therapy or acquire resistance. Understanding and overcoming mechanisms of resistance to antibody drugs, in particular those common to antibody drugs as a class, holds promise to improve cancer immunotherapy. This talk will discuss how activating and inhibitory Fc gamma receptors (FcγR)–the “antibody checkpoints”–regulate antibody-induced antitumor immunity, and in particular, how targeted blockade of the sole-known inhibitory FcγRIIB may help overcome resistance and boost activity of clinically validated and emerging anti-cancer antibodies.

09:05 The Development of KY1043, a Highly-Differentiated PD-L1-Based IL-2Ra-Biased Immunocytokine

McCourt_MatthewMatthew McCourt, BSc, Vice President, Immuno-Oncology Discovery, Kymab Ltd.

Kymab is developing KY1043, an immunocytokine that combines an attenuated IL-2 molecule with our proprietary PD L1-blocking antibody. KY1043 is designed to remove checkpoint inhibition by preventing PD-1 signalling, deliver localized immune activation at the tumour site, and activate immunological memory against the tumour. In preclinical studies, KY1043 has been shown to eradicate tumours and lead to long-term survival, while avoiding the serious adverse events typically associated with systemic delivery of IL-2.

09:35 Problem-Solving Breakout Discussions*

TABLE 7: Challenges and Immunosuppressive Mechanisms that Restrict Anti-Tumour Functions of Monoclonal Antibodies in the Tumour Microenvironment 19

Moderator: Stephen A Beers, PhD, Professor of Immunology and Immunotherapy, Centre for Cancer Immunology, University of Southampton

  • Selection of target antigens for antibody immunotherapy of solid tumours
  • Target antigen heterogeneity and its influence on anti-tumour functions of antibodies; escape mechanisms.
  • Importance of affinity to the target antigen and to Fc receptors for:
    • tissue penetration
    • anti-tumour functions
  • Interrogating the cytokine environment and the immunosuppresive cell populations infiltrating tumours

TABLE 8: Management of Checkpoint Refractory Patients

 Moderator: David Mills, PhD, Director, Oncology, Therapeutics Research, Zymeworks

  • How to manage CPI resistant patients
  • Predicting, preventing and monitoring CPI resistance
  • New targets beyond PD-1/PD-L1 and CTLA-4
  • Assays to assess multiple mechanism-of-action: in vitro, mouse, and monkey
  • Hitting multiple targets: combinations vs. multi-specific antibodies

10:30 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)


KEYNOTE PRESENTATIONS: CHALLENGES AND BENEFITS OF IMMUNOCYTOKINES
11:15
Development of Novel Immunocytokines for Cancer Immunotherapy

Christian Klein, PhD, Head, Oncology Programs, Head, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development
	(pRED), Roche Innovation Center ZurichChristian Klein, PhD, Head, Oncology Programs, Head, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Zurich

High-dose IL-2 is approved for patients with metastatic melanoma and renal cell cancer, but is associated with significant toxicity. This presentation will give an overview of the engineering and development of IL-2 variant-based immunocytokines, like FAP-IL2v and novel generation immunocytokines, as well as of the combination of these agents for combination cancer immunotherapy.

11:45 Novel Formats for Antibody-Cytokine Fusion Proteins: Impact on Performance

Christian Klein, PhD, Head, Oncology Programs, Head, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development
	(pRED), Roche Innovation Center ZurichDario Neri, PhD, Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich)

Antibody-cytokine fusions allow the selective delivery of immunomodulatory stimuli to the site of disease, helping spare normal organs. In this lecture, I will show the impact of the format and architecture of antibody-cytokine fusions on therapeutic performance, both clinically and preclinically.

12:15 Vps34 Inhibitors Increase the Efficacy of Anti-PD1/PD-L1 Immunotherapy by Modulation of the Tumor Inflammatory Landscape

DeMilito_AngeloAngelo De Milito, PhD, Director, Tumor Biology and Therapeutics, Sprint Bioscience

New combination strategies are needed to increase therapeutic efficacy of anti-PD-1/PD-L1-based immunotherapy. Defective autophagy has been associated with a proinflammatory response regulating innate immunity. We found that genetic and pharmacological inhibition of the lipid-kinase Vps34 reduce tumor growth and increase the infiltration of immune cells, including NK, CD8+ and CD4+ T effector cells in melanoma and colon carcinoma murine tumors. Treatment with small molecule Vps34 inhibitors (Vps34i) induces an inflamed tumor microenvironment, characterized by the upregulation of pro-inflammatory cytokines and significantly improved the efficacy of anti-PD-L1/anti-PD1 therapy.

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:45 Dessert Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

TARGETING RESISTANCE: MACROPHAGES, MYELOID-DERIVED SUPPRESSOR CELLS AND CHECKPOINTS
Auditorium VIII

14:15 Chairperson’s Remarks

Björn Frendéus, PhD, CSO, BioInvent International AB

14:20 Modifying the TME to Overcome Resistance to Immunotherapy

Tesi_R_JRJ Tesi MD, CEO/CMO INmune Bio, La Jolla

Resistance to immunotherapy is common and frustrating for patients and their clinical teams. Immunotherapy resistance mechanisms have a different etiology from resistance to chemotherapy. Targeting the cause of the immunologic resistance allows the re-use of the first-line immunotherapy. Two case studies will be presented: i) reversing resistance to immune checkpoint inhibitors caused by elevated MDSC and ii) reversing resistance to trastuzumab in women with HER2+ breast cancer.

14:50 Selectively Inhibiting CD47 in the Tumor Microenvironment

Fischer_NicolasNicolas Fischer, PhD, Head, R&D, Novimmune

Restricting inhibition of the CD47-SIRPa signaling axis to the microenvironment using a bispecific antibody approach enables a better safety and pharmacokinetic profile when compared to monospecific approaches. This mode of action has been validated preclinically against different tumor-associated antigens covering both hematological and solid tumors. The latest development of this selective targeting approach, as well as a clinical update on the most advanced program, will be provided.

15:20 Targeting Tumor-Associated Macrophages to Improve Cancer Immunotherapy

minhong_yanMinhong Yan, PhD, Principal Scientist, Molecular Oncology, Genentech, Inc.

In homeostasis, apoptosis is immunologically quiescent because dying cells are disposed rapidly by tissue macrophages. As a potential way to evade immunosurveillance, tumor-associated macrophages (TAMs) may leverage the same clearance mechanism to avoid innate immune sensing of dying tumor cells. We showed that disabling the dying cell clearance transforms the tumor microenvironment towards an immunogenic milieu, which in turn, enhances the antitumor effect of the PD-1/PD-L1 blockade.

15:50 Efficacy in Syngeneic Models using a PD-L1 Affimer Antagonist in Combination with a Small Molecule Inducer of the Innate Immune System

Basran_Amrik_NAB2Amrik Basran, PhD, CSO, Avacta Life Sciences

Affimer therapeutics are based on the human protein Stefin A, a small (12 kDa) intracellular protease inhibitor. Using phage display, we have generated high affinity antagonists to important check-point inhibitors, such as PD-L1. Our PD-L1 antagonist (AVA04 Fc) in combination with a small molecule inducer of the innate immune system (PT-100), demonstrated efficacy, tumour regression in several individuals, as well as immunity to rechallenge with the original mouse tumour cell line.

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

REPROGRAMMING THE MICROENVIRONMENT/THE INNATE IMMUNE SYSTEM/GLYCO-IMMUNE CHECKPOINTS
Auditorium VIII

17:00 Optimizing Bispecific 4-1BB Agonists for Tumor-Conditional T Cell Activation

David Mills, PhD, Director, Oncology, Therapeutics Research, Zymeworks

Although checkpoint blockade has revolutionized cancer treatment, some patient subsets remain resistant. The broader success of immunotherapy likely requires combinatorial approaches and targeting alternative mechanisms. In particular, suppressive myeloid cell accumulation reduces effector lymphocyte fitness, predicts immunotherapy resistance, and is negatively prognostic. We have undertaken a novel approach to reinvigorate anti-tumor immunity, and will discuss characterization of multifunctional, bispecific antibodies that antagonize suppressive myeloid cell activities and costimulate T cell differentiation.

17:30 TLR Agonist NKTR-262 Immunotherapy Combination with Bempegaldesleukin (NKTR-214) Harnessing Innate and Adaptive Immune System for the Treatment of Solid Tumors

Kivimae_SaulSaul Kivimäe, PhD, Head, In Vivo Pharmacology Function, Research Biology, Nektar Therapeutics

NKTR-262 is a novel TLR agonist therapeutic designed to deliver intratumoral TLR7/8 engagement and is currently evaluated in Phase 1 dose escalation study with bempegaldesleukin, a CD122-preferential IL-2 pathway agonist. NKTR-262 combination treatment with bempegaldesleukin is designed to provide a synergistic effect of localized intratumoral innate immune stimulation with systemic, sustained T cell activation for comprehensive anti-tumor immune activation, mimicking a natural immune response.

18:00 Aberrant Glycosylation in Breast Cancer Results in Modulation of the Immune Microenvironment

Burchell_JoyJoy Burchell, PhD, Professor, Glyco-oncology, Head, Breast Cancer Biology Lab, Comprehensive Cancer

Centre, School of Cancer and Pharmaceutical Sciences, King’s College London

Cancers have developed a plethora of mechanisms to evade the immune response, including initiating a permissive local environment. For cancer cells to remodel their immune microenvironment, they need to acquire changes that include altering their glycosylation profile. We have shown that the interaction of a tumour-associated glycoform of MUC1, expressed by breast carcinomas with the lectin Siglec-9 found on monocytes and macrophages, can act as such an immune microenvironment remodeling trigger.

18:30 Targeting Immunosuppressive Sialoglycans in the Tumor Microenvironment Using a Novel Therapeutic Modality, EAGLE

Peng_LiLi Peng, PhD, Senior Vice President, Discovery and Early Product Development, Palleon Pharmaceuticals

The glyco-immune checkpoint axis (sialoglycan/Siglec pathway) has emerged as a novel mechanism of cancer immune escape. Here, we described a novel therapeutic modality, a bifunctional antibody-like molecule named EAGLE (Enzyme-Antibody Glyco-Ligand Editing), to target this axis by selectively removing immuno-suppressive terminal sialic acids on tumor cells. We demonstrated that EAGLE treatment led to robust anti-tumor activities and increased immune cell infiltration/activation in syngeneic mouse tumor models.

19:00 End of Modulating the Tumour Microenvironment

* 活動內容有可能不事先告知作更動及調整。

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