Cambridge Healthtech Institute 第1回

Emerging Immuno-Oncology Targets
( がん免疫分野の新たな標的 )

がん免疫療法と併用療法のための新たな標的とパスウェイ
2017年8月31日 - 9月1日 | Sheraton Boston | 米国マサチューセッツ州ボストン

がん免疫分野の新たな標的をテーマにしたこのカンファレンスプログラムでは、免疫調節阻害剤やアゴニストの標的、間質細胞と免疫細胞の標的、合理的な併用免疫療法のための戦略など、新たな研究領域に光が当てられるほか、がん免疫療法と併用療法の新たな標的の発見と検証に向けた前臨床研究やトランスレーショナル研究のケーススタディも披露されます。



Final Agenda


THURSDAY, AUGUST 31

7:45 am Registration & Morning Coffee

IMMUNE CHECKPOINT INHIBITORS: BEYOND PD-L1

8:25 Chairperson's Opening Remarks

Andrea van Elsas, Ph.D., CSO, Aduro Biotech Europe

8:30 TIM-3 Biology in Myeloid Cells and Implications for TIM-3 Blockade in Immuno-Oncology

Xiaomo Jiang, Ph.D., Investigator, Immuno-Oncology, Novartis Institutes for BioMedical Research

TIM-3 has critical roles in tumor-induced immune suppression on a multitude of cell types. TIM-3 blockade to activate immune response and control tumor growth could reflect the combined effects on modulating not only the functional phenotype of dysfunctional effector T cells, but also inhibiting the suppressive activity of various suppressor cells.

9:00 Exploring Checkpoint Biology in Syngeneic Mouse Models

Fiona Sharp, Ph.D., Investigator II, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research

The role of checkpoint proteins in regulating anti-tumor immunity has by now been well established for multiple proteins, including PD-1/PD-L1, LAG-3 and TIM-3. While the cellular and ligand interaction targets for some of these proteins are well defined, our knowledge of these aspects of TIM-3 requires further investigation. Gaining better insight into the key players in TIM-3 biology is central to enhancing the efficacy of this target in the clinic. Our studies have been focused on further exploring the key immune cells involved in TIM-3 controlled anti-tumor immune responses in syngeneic mouse models.

9:30 New Immune Checkpoints for Human Cancer Immunotherapy

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

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

10:00 Coffee Break in the Exhibit Hall (Last Chance for Poster Viewing)

IMMUNOMODULATORY AGONIST TARGETS

10:45 Preclinical and Clinical Activity of the CD27 Agonist Antibody Varlilumab

Tibor Keler, Ph.D., Senior Vice President & CSO, Celldex Therapeutics

In preclinical models, varlilumab's agonist properties that lead to immune activation need to be coupled with its deleterious effect on Tregs to achieve potent antitumor activity across multiple models. A similar profile of immune activation and reduction in Tregs has been observed in cancer patients treated with varlilumab. Significant efforts are underway to correlate these biomarkers with clinical endpoints to inform dose and patient selection.

11:15 Preclinical Evaluation of GITR Ligand

Angie Inkyung Park, Ph.D., Senior Director, Immunotherapy and Stem Cells, OncoMed Pharmaceuticals

A novel single-gene linkerless GITRL trimer fused to an immunoglobulin Fc domain (GITRL-Fc) was generated and tested for its anti-tumor activity in preclinical tumor models. GITRL-Fc showed potent anti-tumor activity in several preclinical tumor models by inducing Th1 biased anti-tumor immunity and reducing Treg-mediated immune suppression. Combination of GITRL-Fc with PD-1/PDL1 blockade significantly reduced the tumor growth in non-inflamed cold tumors. GITRL-Fc can improve cancer treatment by enhancing both innate and adaptive cellular immunity.

11:45 Targeting IDO1 to Enhance Cancer Immunotherapy: Not So Simple After All

Derek A. Wainwright, Ph.D., Assistant Professor, Departments of Neurological Surgery, Microbiology-Immunology, and Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine

IDO1 is canonically-recognized as an inducible enzyme that converts tryptophan into kynurenine. In cancer immunology, IDO1 has been associated with contributing to immunosuppression of the anti-tumor immune response. However, tryptophan depletion and/or kynurenine accumulation does not fully account for IDO1-mediated immune evasion by cancer cells. Utilizing syngeneic and humanized mouse models of glioblastoma (GBM), in addition to the analysis of patient-resected tumors, new aspects of IDO1 will be described.

12:15 pm Sponsored Presentation (Opportunity Available)

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

1:15 Session Break

EMERGING TARGETS FOR COMBINATION IMMUNOTHERAPY

2:25 Chairperson's Remarks

Jennifer Wu, Ph.D., Professor, Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina; CSO, CanCure BioPharma


2:30 KEYNOTE PRESENTATION: Elements of Rational Combination Development in Cancer Immunotherapy

Edward Cha, M.D., Ph.D., Associate Medical Director, Cancer Immunotherapy Franchise, Genentech

The tumor microenvironment plays an important role in inhibiting the propagation of effective cancer immunity. Although PD-L1 is a critical source of immune suppression, additional elements in this environment also determine whether cancers successfully are eradicated or evade the immune response. This talk will focus on approaches to targeting immune escape mechanisms through novel agents and combinations, and on clinical designs that support more efficient discovery.

3:00 Pharmacodynamics and Antitumor Activity of the Adenosine 2A Receptor Antagonist AZD4635

Rich Woessner, Ph.D., Principal Scientist, IMED Oncology, AstraZeneca Pharmaceuticals

AZD4635 is a potent and highly selective antagonist of adenosine-mediated A2A receptor signaling, and inhibits T-cell function in ex vivo assays. In murine tumor models, oral administration of AZD4635 increases the expression of genes associated with immune activation, increases expression of co-stimulatory markers on antigen presenting cells, and enhances the antitumor activity of anti-PD-L1 antibody treatment. AZD4635 is in clinical evaluation as a single agent and in combination with the anti-PD-L1 antibody durvalumab.

3:30 Sponsored Presentation (Opportunity Available)

4:00 Refreshment Break

4:30 Beyond Immune Checkpoint: Targeting Soluble NKG2D Ligands for Cancer Immunotherapy

Jennifer Wu, Ph.D., Professor, Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina; CSO, CanCure BioPharma

Human tumor-derived soluble NKG2D ligand sMIC is highly immune suppressive and thus an emerging target for cancer immunotherapy. Using a clinically relevant mouse model, we show that therapy with the non-blocking sMIC-neutralizing antibody resulted in effective debulking primary tumors and eliminating metastases. Neutralizing sMIC also synergistically enhanced tumor response to PD-1 and CTLA4 immune checkpoint blockade therapy. These findings launched a new avenue of combination cancer immunotherapy.


5:00 KEYNOTE PRESENTATION: Cancer Immunotherapy beyond PD-1

Andrea van Elsas, Ph.D., CSO, Aduro Biotech Europe

Checkpoint inhibitors have set a new clinical paradigm, but a majority of patients with advanced cancer do not respond. New pathways targeting T cells and other cells in the tumor microenvironment are discussed. In addition, the potential use of active immunization approaches in combination therapy will be highlighted with the aim to extend the clinical benefit of immune oncology to more patients.

5:30 Development of TGFβ Inhibitors for Immune-Oncology

Rikke Holmgaard, Ph.D., Senior Research Scientist, Eli Lilly

The transforming growth factor β (TGFβ) signaling pathway is a pleiotropic cellular pathway that plays a critical role in cancer. In fact, aggressive tumors are typically associated with high ligand levels and thus associated with poor prognosis in various tumor types. Here we describe the identification of inhibitors targeting the TGFβ pathway and provide proof of concept data supporting the role of TGFβ in cancer and the utility of targeting the TGFβ pathway.

6:00 End of Day

6:00 Dinner Short Course Registration*

Recommended Dinner Short Courses*

SC3: Study Design and Statistical Data Analysis of Flow Cytometry Assays for Cancer Immunotherapy

SC4: CRISPR/Cas9 Applications in Immunotherapy

*Separate registration required, please click here for more information.


FRIDAY, SEPTEMBER 1

8:00 am Registration and Morning Coffee

EMERGING TARGETS FOR BISPECIFIC AGENTS

8:25 Chairperson's Opening Remarks

Shane Olwill, Ph.D., Vice President, Head of Development & Immuno-Oncology, Pieris Pharmaceuticals GmbH

8:30 Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific PRS-343 for Tumor Localized Activation of the Immune System

Shane Olwill, Ph.D., Vice President, Head of Development & Immuno-Oncology, Pieris Pharmaceuticals GmbH

PRS-343 is a bispecific monoclonal antibody/Anticalin fusion protein comprised of a HER2 tumor-targeting mAb genetically linked to a potent Anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes (TILs), and is therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.

9:00 Dual Targeting Bispecific Antibodies Selectively Block Innate Immune Checkpoint Receptor CD47 on Tumor Cells

Stefano Majocchi, Ph.D., Research Scientist, Novimmune SA

CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. We generated dual-targeting bispecific antibodies capable of selective inhibition of CD47 on malignant cells through co-engagement of a tumor-associated antigen (TAA). This dual-targeting approach exploits an innovative cancer immunotherapy mechanism while avoiding a poor pharmacological half-life and potential hematological toxicities which are observed when CD47 is indiscriminately blocked. Such bispecific antibodies lead to TAA-dependent cancer cell killing through ADCP and ADCC in vitro and show anti-tumor activity in vivo associated with long pharmacokinetic half-life and absence of toxicity.

9:30 Predicting the Efficacy and Safety Profile of ImmTAC™ Molecules: The Preclinical Challenge

Martina Canestraro, Ph.D., Senior Scientist, Preclinical Biology, Immunocore, Ltd.

ImmTAC™ molecules consist of an affinity enhanced T cell receptor fused to an anti-CD3 specific scFv. Since both ends of the molecule are human specific, standard species tox models are not appropriate for ImmTAC safety testing. This presentation will provide an overview of our technology and of the in vitro preclinical approach that was used to predict the safety and efficacy profile of our most advanced molecule IMCgp100, currently in Phase II clinical trials for the treatment of cutaneous and uveal melanoma.

10:00 Coffee Break

IDENTIFYING AND TARGETING TUMOR NEOANTIGENS

10:30 Discovery and Development of Novel Immunogenic Tumor Neoantigens for the Treatment of Solid Tumors

Philip M. Arlen, M.D., President & CEO, Precision Biologics, Inc.

Immunogenic neoantigens were derived from a membrane preparation of pooled allogeneic colorectal cancer from patients undergoing surgery. Membrane fractions were isolated and tested for immunogenicity and utilized in a clinical trial in patients with chemotherapy refractory metastatic colorectal cancer. A positive correlation was observed in patients who were able to mount and sustain IgG responses to vaccine. Antibodies were screened using this vaccine and tested for sensitivity, specificity, and anti-tumor function. Neoantigens were identified in colon cancer with these functional antibodies.

11:00 Antigen Cascade - Using Self-Antigen Directed Vaccines to Target Neoepitopes

Christopher R. Heery, M.D., CMO, Bavarian Nordic

Dr. Heery will discuss various strategies capable of inducing specific T cell responses against tumor associated antigens. The result of that T cell mediated killing is antigen cascade, a process by which the immune response can broaden and deepen against additional antigenic targets on the tumor cells. Dr. Heery will discuss the preclinical and clinical evidence supporting Antigen Cascade, new tools to evaluate this process, and how this data might inform future trials and clinical treatment strategies.

11:30 High-Throughput Functional Screening of Neoantigens for Vaccines and TCR-Based Adoptive T Cell Therapies

Dolores J. Schendel, Ph.D., CEO & CSO, Medigene AG

Neoantigens are an important class of highly specific target molecules for various immunotherapies. In transiting from identification of mutant peptides by NGS and prediction of binding to HLA allotypes, Medigene explores high throughput technologies to functionally verify that predicted neoantigens do in fact lead to T cell recognition. Our rapid methods bypass the need for patient cells, overcoming logistical restrictions for determining the true immunogenicity of predicted neoantigens.

12:00 pm Close of Emerging Immuno-Oncology Targets





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