Cambridge Healthtech Institute 第1屆

Intrinsic and Acquired Resistance to Immunotherapy

( 免疫療法的內在及後天阻力 )

癌症免疫療法策略及無反應者之預測生物標記


2018年6月12 - 13日 | Westin Boston Waterfront | 馬薩諸塞州波士頓

免疫療法、特別是免疫檢查點抑制劑的進步,大幅改變特定癌症治療的方法。然而,作為單一療法使用時,由於內在及後天阻力等原因許多病患對治療無法產生反應,或是最初雖有效果、但後來又出現阻力。本會議以免疫療法的內在及後天阻力為主題,聚焦阻力機制、免疫回避中表觀遺傳學及腫瘤微環境的作用、長期腫瘤樣本搜集以發現生物標記反應的重要性等議題,並安排免疫療法專家針對、克服阻力、改善病患結果的預測及治療策略等議題進行分享。

Final Agenda

Tuesday, June 12

1:00 pm Conference Registration

 

MECHANISM OF NON-RESPONSE: RESISTANCE OR LACK OF EFFICACY

1:55 Chairperson's Opening Remarks

Pawel Kalinski, MD, PhD, Professor, Oncology; Vice-Chair, Translational Research, Roswell Park Cancer Institute

2:00 Targeting the Tumor Microenvironment: Understanding Resistance Mechanisms in IO-Refractory Patients

Zhen Su, MD, MBA, CMO, North America, EMD Serono, Inc.

With the advent of IO therapy in oncology, we have seen significant improvements in the response rates and overall survival of cancer patients. However, the challenges to identify responsive patient populations, as well as understand mechanisms of resistance, continue to dampen our progress. Recent advances and preliminary combination regimens present a promising path forward; however, will this be enough to ensure durable responses in patients, especially in real-world settings?

2:30 The Stromal Microenvironment in Cancer Immunology and Immunotherapy

Shannon J. Turley, PhD, Principal Scientist, Cancer Immunology, Genentech

This presentation will cover: understanding the role of stromal cells in the tumor microenvironment and the effect of cross-talk with immune cells; analyzing factors correlating with resistance to atezolizumab and reverse-translating this information to provide meaningful preclinical insights; and building tools to study mesenchymal cells and their impact on immuno-oncology across tumor types.

3:00 Sponsored Presentation (Opportunity Available)

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:25 Chairperson's Remarks

Pawel Kalinski, MD, PhD, Professor, Oncology; Vice-Chair, Translational Research, Roswell Park Cancer Institute

4:30 COX2-PGE2-Orchestrated Secondary Suppression in the Course of Immunotherapy

Pawel Kalinski, MD, PhD, Professor, Oncology; Vice-Chair, Translational Research, Roswell Park Cancer Institute

Immune checkpoint inhibition (ICI) provided new effective treatment option for patients with many types of advanced cancer, but the majority of patients still show primary or secondary resistance to ICI. The effectiveness of ICI and many other forms of cancer immunotherapy is regulated at the level of tumor microenvironments (TME) by the balance between type-1 immune cells, such as CD8+ cytotoxic T cells (CTLs), Th1 and NK cells and suppressive cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). We observed that the activation of CTLs or NK cells in TMEs of human cancers, results in a strong mobilization of "secondary" suppression, mediated by activated MDSCs and their production of COX2, IDO, and IL-10, which suppress CTL function.

5:00 Antigen Presentation Defects and Resistance to Checkpoint Inhibitor Therapy

Ryan J. Sullivan, MD, Assistant Professor, Hematology & Oncology, Massachusetts General Hospital; Assistant Professor, Medicine, Harvard Medical School

Immune checkpoint inhibitor therapy leads to durable responses in a significant minority of patients with solid tumors and may improve overall survival in select diseases. However, most patients will not benefit and a significant percentage of patients who do respond, will develop acquired resistance. Proper antigen presentation is critical for initial and ongoing tumor immunity, and impaired antigen presentation machinery is an important mechanism of both intrinsic and acquired resistance.

5:30 Acquired Resistance to Immune Modulation in Lung Cancer

Katerina Politi, PhD, Associate Professor, Pathology, Yale School of Medicine

Immune checkpoint inhibitors have transformed the treatment landscape for lung cancer. However, most patients whose tumors initially respond to treatment eventually develop drug resistance disease. Emerging data indicate that lung tumors can escape treatment with immune checkpoint inhibitors by altering HLA Class I antigen presentation. Insights into how HLA Class I antigen presentation is disrupted in immune checkpoint inhibitor resistant tumors is critical to finding strategies to overcome drug resistance.

6:30 Dinner Short Course*

SC3: Multiplexed Analysis of Tumor Tissues Using Spatially Resolved and Quantitative Platforms

*Separate registration required

Wednesday, June 13

7:25 am Interactive Breakout Discussion Groups with Continental Breakfast

This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

COMBINATION IMMUNOTHERAPY TO OVERCOME RESISTANCE

8:25 Chairperson's Remarks

Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development; CMO, Merck Research Laboratories

8:30 PD-1 Antibody Therapy: Approaches to Primary Resistance

Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development; CMO, Merck Research Laboratories

PD-1 antibody therapy has shown broad spectrum activity across an array of solid malignancies. Informative biology helped identify those cancer types for initial exploration. A majority of patients however appear to exhibit primary resistance to such therapy. Precision medicine approaches help identify those patients most likely to respond to monotherapy, those patients who should be considered for further clinical research and potentially suggest combination approaches to address primary resistance.

9:00 Intrinsic Resistance to Immune Checkpoint Therapy and Potential Approaches to Overcome Resistance in Genitourinary Malignancies

Jianjun Gao, MD, PhD, Assistant Professor, Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center

This presentation will focus on both genomic and tumor microenvironment resistance mechanisms of immune checkpoint therapy; rationale for designing combinational approaches to overcome resistance using genitourinary malignancies including prostate, kidney and bladder cancer as models; and preliminary data on some of these combination therapy clinical trials.

9:30 Combination Immunotherapy Strategies to Overcome Resistance to PD-1 Therapy

Osama Rahma, MD, Assistant Professor, Medicine, Dana-Farber Cancer Institute, Harvard Medical School

Primary and adaptive resistance to PD-1 therapy represents a major challenge in immunotherapy drug development. Primary resistance could be driven by a defect in antigen presentation or priming the T-cells while secondary resistance could be related to the co-expression of many immune checkpoints. This presentation will explore immunotherapy combination strategies to overcome both primary and secondary resistance.

10:00 Networking Coffee Break

 

EMERGING TARGETS AND THERAPEUTIC STRATEGIES TO ADDRESS RESISTANCE

10:30 Targeting TGF-Beta in Intrinsic and Acquired Resistance to Cancer Immunotherapy

Laszlo Radvanyi, PhD, Senior Vice President & Senior Global Scientific Advisor, Immuno-Oncology, EMD Serono

11:00 Sponsored Presentation (Opportunity Available)

11:30 Investigating the Role of Innate Immunity in Adaptive Resistance to Cancer Immunotherapy

Brent A. Hanks, MD, PhD, Assistant Professor, Cancer Immunology/Immunotherapy, Duke Cancer Institute

We will explore recently identified mechanisms that cancers have evolved to suppress T cell-mediated immunity as an adaptive response to checkpoint inhibitor immunotherapy. Further discussion will address strategies to inhibit these mechanisms and augment the efficacy of currently available checkpoint inhibitor regimens.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

 

IMMUNE MONITORING: BIOMARKERS OF RESPONSE AND RESISTANCE

1:25 Chairperson's Remarks

Wendy Winckler, PhD, Executive Director, Next Generation Diagnostics, Novartis Institutes for Biomedical Research

1:30 Response and Resistance in CAR-T Therapy

Wendy Winckler, PhD, Executive Director, Next Generation Diagnostics, Novartis Institutes for Biomedical Research

2:00 Molecular Determinants for Sensitivity and Resistance to Immunostimulatory Therapies in Cancer

Kurt Schalper, MD, PhD, Assistant Professor, Pathology and Medicine (Medical Oncology), Yale School of Medicine

2:30 Cancer Immunotherapy Biomarkers for Selection and Monitoring

Glen J. Weiss, MD, MBA, Clinical Associate Professor, University of Arizona College of Medicine, Phoenix

There are now multiple monoclonal antibody immunotherapies available for clinical use to treat advanced cancers. However, just a fraction of these patients experience an impressive durable response. How are these therapies selected and how is efficacy monitored? This lecture will highlight current data on biomarkers being used and evaluated for treatment selection and monitoring.

3:00 Close of Conference

* 活動內容有可能不事先告知作更動及調整。