Cambridge Healthtech Institute’s 4th Annual

Immuno-Oncology Biomarkers
( 癌症免疫疗法之并用免疫疗法 )

Predictive Biomarkers and Companion Diagnostics

2019年8月5日~6日



As pharmaceutical and biotechnology companies increase their investment in immuno-oncology programs to facilitate rapid development of novel immunotherapies, there is increasing pressure to discover and validate relevant biomarkers. Cambridge Healthtech Institute’s Fourth Annual Immuno-Oncology Biomarkers conference will bring together biomarkers experts from industry and academia to address rapid development of predictive and prognostic IO biomarkers, utility of these biomarkers in clinical trials, and their potential as companion diagnostics.

Final Agenda

8月5日(一)

7:30 am Registration Open and Morning Coffee

LIQUID BIOPSY FOR IMMUNO-ONCOLOGY

8:25 Chairperson’s Opening Remarks

Theresa Whiteside, PhD, Professor, Pathology, Immunology & Otolaryngology, Hillman Cancer Center, University of Pittsburgh School of Medicine

8:30 Tumor-Derived Exosomes as Potential Biomarkers of Cancer Progression and Immune Dysfunction in Cancer

Theresa Whiteside, PhD, Professor, Pathology, Immunology & Otolaryngology, Hillman Cancer Center, University of Pittsburgh School of Medicine

Tumor-derived exosomes in plasma of cancer patients are emerging as promising non-invasive correlates of cancer progression or response to therapy. To study the impact of melanoma cell-derived exosomes (MTEX) on human immune cells and melanoma progression, we isolated MTEX from total exosomes in plasma by immune capture with Abs. MTEX were highly enriched in immunosuppressive receptors/ligands. Non-MTEX (non-malignant cell-derived exosomes) were enriched in immunostimulatory proteins. The ratio of stimulatory/suppressive cargo components in subsets of circulating exosomes in melanoma determines the exosome capability to modulate immune cell responses and impact disease plasma-derived exosomes in patients with cancer emerge not only as surrogates of the tumor but also as biomarkers of immune competence and potentially as biomarkers of response to immunotherapies.

9:00 KEYNOTE PRESENTATION: Circulating Exosomes and Their Cargo as a Source of Tumor Antigens

Samir Hanash, MD, PhD, Director, McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center

We have investigated circulating exosomes and their cargo as a source of antigens associated with the immune response in pancreatic ductal adenocarcinoma and lung cancer using in-depth mass spectrometry resulting in the identification of a large repertoire of tumor antigens that induce antibody response together with exosome hallmark proteins. The relevance of these antigens as diagnostic or predictive markers, and the role of exosomes in inducing inhibition of serum-mediated complement-dependent cytotoxicity towards cancer cells will be presented.

9:30 Blood-Based Biomarkers of Response and Immune-Related Adverse Events During Immune Checkpoint Blockade

Genevieve Boland, MD, PhD, Assistant Professor, Surgery; Director, Melanoma Surgery Program, Massachusetts General Hospital

Immune checkpoint inhibitors (ICI) enhance anti-tumor immune responses and have unique but acceptable toxicities. The mechanism of ICI response can create immune targeting of self-antigens causing immune-related adverse effects (irAEs). Blood-based analysis allows interrogation of multiple sites of treatment and toxicity simultaneously. We are utilizing blood-based biomarkers to predict and define irAEs to allow maximal treatment without undermining shared mechanisms of irAEs and clinical responses.

10:00 Coffee Break

PREDICTIVE BIOMARKERS FOR IMMUNO-ONCOLOGY

10:30 Predictive Biomarkers for Immunotherapy in Non-Small Lung Cancer

Fred R. Hirsch, MD, PhD, Professor, Medicine, Icahn School of Medicine at Mount Sinai; Executive Director, Clinical Institute for Lung Cancer, Mount Sinai Health Care

Immunotherapy for patients with lung cancer is promising and about 20-40% of patients with advanced NSCLC will benefit from these treatments. However, a challenge is how to select the patients who will benefit. PD-L1 IHC is the assay used in clinical trials for selecting the patients and depending on cut-off for “positive” and “negative” tumors, the assay has demonstrated predictive value, but is not perfect. In order to compare the different PD-L1 assays’ performance, the Blueprint Project was undertaken, and showed that three assays (SP263, Dako 28-8 and Dako 22C3) performed very similar, while SP142 performed differently. The Blueprint Project will be discussed as well as the role of tumor mutation burden (TMB)’s predictive value for outcome of immunotherapy. Also, some future potential biomarkers will be discussed.

11:00 Possible Use of Immunoprofiling to Stratify or Direct Combination Immunotherapy

Bernard A. Fox, PhD, Chief, Laboratory of Molecular and Tumor Immunology, Providence Health & Services; CEO, UbiVac

11:30 Phenotyping the Tumor Microenvironment with Advanced Tissue-Based Muliplexing Assays

Katir Patel, PhD, Field Applications Manager, Ultivue

The benefits of multiplex immunohistochemistry assays for tissue analysis are numerous. High-level multiplexing, whole slide imaging, workflow compatibility, and spatial analysis are all requirements for effective multiplex IHC solutions. Ultivue’s inSituPlex® technology addresses each of these needs to enable researchers to unmask the true biology of tissue samples.

12:00 pm Luncheon Presentation to be Announced

12:30 Session Break

GENOMIC BIOMARKERS IN IMMUNOTHERAPY DEVELOPMENT

1:25 Chairperson’s Remarks

Theresa Whiteside, PhD, Professor, Pathology, Immunology & Otolaryngology, Hillman Cancer Center, University of Pittsburgh School of Medicine

1:30 The Cancer Genome’s Influence on Immunotherapy

Nadeem Riaz, MD, Associate Director, Immunogenomics and Precision Oncology Platform, Radiation Oncology, Memorial Sloan Kettering Cancer Center

We will review data showing the importance oftumor mutation burden in predicting outcomes to checkpoint blockade therapy. We will subsequently discuss emerging genetic features associated with response to therapy including microsatellite instability, HLA genotype, tumor clonality, and neo-antigen modeling among others.

2:00 Harnessing Immune Gene Signatures for Patient Prognosis and Discovery of Tumor Immune Evasion Tactics

Lance D. Miller, PhD, Associate Professor, Cancer Biology; Director, Breast Cancer Center of Excellence; Co-Director, Cancer Genomics Shared Resource, Wake Forest Baptist Comprehensive Cancer Center

Within the global transcriptome of solid tumors are gene signatures that reflect the relative abundance of tumor-infiltrating leukocytes. These immune gene signatures correlate with patient outcomes and can be leveraged within a statistical framework to explore tumor-immune interactions. In this talk, I will discuss the prognostic interplay between immune gene signatures and tumor mutational burden in breast cancer and describe early results of a pan-tumor bioinformatics screen to identify novel mechanisms of tumor immune evasion.

2:30 Sponsored Presentation (Opportunity Available)

3:00 Breakout Discussion Groups and Refreshment Break

BIOMARKERS TO GUIDE COMBINATION IMMUNOTHERAPY

4:00 KEYNOTE PRESENTATION: TMB/GEP Dual Biomarker Strategy for Personalized Checkpoint Blockade Combination Immunotherapy

Jianda Yuan, MD, PhD, Senior Director, Translational Oncology, Merck

Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy. Combination approaches are the keys to improving clinical response. Tumor mutational burden (TMB) and gene expression profile (GEP) are emerging biomarkers predicting patient response. Dual TMB/GEP biomarkers allow us to understand novel translational biomarkers to stratify patients effectively for personalized cancer immunotherapy.

4:30 Is There a Role for Biomarkers in this Era of Combination Immunotherapy?

Kathleen M. Mahoney, MD, PhD, Clinical Instructor, Beth Israel Deaconess Medical Center; Research Fellow, Dana-Farber Cancer Institute

Combinations with PD-1 immune checkpoints such as chemotherapy, ipilimumab or VEGF receptor tyrosine kinase inhibitor can improve response rates and overall survival in some tumors. In the upcoming years, the mechanisms of PD-1 resistant cancer found in patients will be molded by the selective pressures of these therapies. Many clinical trials have investigated the toxicity and efficacy of combining PD-1 pathway blockade with other therapies. Yet few randomized Phase II studies involving immune checkpoints have been designed to develop predictive biomarkers for these therapies. Biomarker-driven early phase trials are needed for designing Phase III trials to prospectively validate (protein or gene signature-based) biomarkers for monotherapy or combination immunotherapy, if the pendulum is to swing back toward the development of personalized therapies with fewer toxicities.

5:00 Close of Day

8月6日(二)

7:30 am Registration Open and Morning Coffee

TUMOR IMMUNE MICROENVIRONMENT CHARACTERIZATION

8:25 Chairperson’s Remarks

Shahram Salek-Ardakani, PhD, Senior Director, Cancer Immunology, Pfizer

8:30 Image Mass Cytometry to Characterize the Tumor Immune Microenvironment

Maria Paola Serra, PhD, Senior Scientist, Pathology, AstraZeneca

Image Mass Cytometry (IMC) is a novel technique for tissue imaging that enables simultaneous quantification of more than 30 biomarkers with subcellular resolution, preserving cell morphology. This large panel applied to cancer samples allows delineation of cell subpopulations, cell-cell interactions and the localization of immune cell infiltrates to evaluate host response. IMC analysis can be performed in parallel with conventional mass spectrometry imaging.

9:00 Single Cell Analyses Reveal Important Regulatory Mechanism in Cancer Immunotherapy

Xin Yu, PhD, Scientist, Immuno-Oncology, Amgen

Checkpoint inhibitor-based immunotherapies (such as anti-PD1) have achieved impressive success in treating different types of tumors. However, only a subset of patients derives clinical benefit. Given that tumor-infiltrating lymphocytes are highly heterogeneous, which might contribute to diverse responses to different cancer immunotherapies, we performed single-cell RNA sequencing analysis to characterize immune cells inside colorectal carcinoma, adjacent normal mucosa and peripheral blood. Our analyses identified a distinct BHLHe40+ Th1-like CD4 T cell subset that was preferentially enriched in tumors of microsatellite-instable (MSI) patients, which might explain their favorable response rates to immune-checkpoint blockade. Furthermore, our data identified potential novel regulatory molecules such as IGFLR1 for several T cell subsets inside colorectal tumors. These discoveries will shed light on the development of effective immunotherapeutic strategies.

9:30 Automation Meets Cell Separation: Primary Cell Isolation for Immuno-Oncology Assays

Lotta Räty, Product Manager, Cell Separation Automation, Marketing, Miltenyi Biotec GmbH

Conclusive and relevant assay results depend on reliable sample processing, including cell separation and tumor dissociation. We have developed flexible automated solutions for primary cell isolation from various starting materials to ensure the best fit for every drug discovery program.

9:45 Presentation to be Announced

10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

10:55 Chairperson’s Remarks

Shahram Salek-Ardakani, PhD, Senior Director, Cancer Immunology, Pfizer

11:00 The Role of Tumor-Resident Phagocytic Cells for Anti-Tumor Immunity

Stefani Spranger, PhD, Assistant Professor, Biology, Koch Institute for Integrative Cancer Research, MIT

11:30 Dynamic Analysis of Human Natural Killer Cell Response at Single-Cell Resolution in B-Cell Non-Hodgkin Lymphoma

Tania Konry, PhD, Assistant Professor, Pharmaceutical Sciences, Northeastern University

Natural Killer (NK) cells are phenotypically and functionally diverse lymphocytes that recognize and kill cancer cells. To correlate genetic signatures with functional anti-lymphoma activity, we developed novel microfluidic technology to characterize functional heterogeneity in cytolysis of primary cells from b-NHL patients. Taken together, our combined genetic and microfluidic analysis demonstrate b-NHL cell sensitivity to primary and therapeutic NK cell-based cytotoxicity, associated with significant heterogeneity in the dynamic interaction at single cell level.

12:00 pm Close of Immuno-Oncology Biomarkers

* 活动内容有可能不事先告知作更动及调整。

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