Quantitative Immune Profiling and Immune Monitoring Icon

Cambridge Healthtech Institute’s Inaugural

Quantitative Immune Profiling and Immune Monitoring

Immunophenotyping and Immunosequencing for Immuno-Oncology Biomarker Discovery
August 28-29, 2017 | Sheraton Boston | Boston, MA


Advances in immuno-oncology promise to revolutionize cancer treatment. However, many patients do not respond to immunotherapy. Immune profiling promises to identify biomarkers that predict response to immunotherapy and to help monitor its progress. Cambridge Healthtech Institute’s Inaugural Quantitative Immune Profiling and Immune Monitoring meeting will cover quantitative approaches to assess the state of the immune system, profile the tumor microenvironment and peripheral blood, determine tumor mutational burden and profile neoepitopes, and develop predictive and response biomarkers.



Final Agenda


MONDAY, AUGUST 28

7:30 am Registration & Morning Coffee

IMMUNOPHENOTYPING: BIOMARKER DISCOVERY AND VALIDATION FOR IMMUNO-ONCOLOGY

8:25 Chairperson’s Opening Remarks

Morganna Freeman, DO, FACP, Associate Director, Melanoma & Cutaneous Oncology Program, The Angeles Clinic and Research Institute


8:30 KEYNOTE PRESENTATION: The New Precision Medicine: The Role of Dynamic Tumor and Immune Sampling in Immunotherapy

Morganna Freeman, DO, FACP, Associate Director, Melanoma & Cutaneous Oncology Program, The Angeles Clinic and Research Institute

Immunotherapy has revolutionized the oncology treatment landscape, and as therapies evolve, there is a recognized need for biomarkers to inform the likelihood and duration of response. Radiologic assessments, i.e. RECIST, may be supplanted by biologically relevant markers in order to develop timely, cost-effective, and potentially personalized therapy. This presentation will review dynamic tumor and immune sampling as early markers of clinical response and their emerging role in clinical decision making.

9:00 Intersection of Host Factors and Novel Biomarkers for Immunotherapy

Adil Daud, M.D., Professor, Hematology/Oncology, University of California, San Francisco; Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center

T cell exhaustion is thought to be a critical mechanism for immune evasion by tumors. While PDL-1 immunohistochemistry provides a marker for the presence of tumor reactive T cells, we have developed a direct profiling method that involves extracting and profiling T cells directly from the tumor microenvironment. This flow-based method enables a dynamic picture of tumor T cell interaction. We describe some of the applications of this method for predicting response to single agent or combination immunotherapy.

9:30 Coffee Break

10:00 In situ Multiparametric Tumor Immunoprofiling for Translational Research in Oncology

Kurt Schalper, M.D., Ph.D., Assistant Professor, Pathology and Medicine (Medical Oncology), Yale School of Medicine

Diverse studies have identified biomarkers associated with clinical benefit to immune checkpoint blockers. However, the clinical use of such tests is limited by their variable performance and restricted understanding of their biological significance. This presentation will cover the use of multiplexed analyses of tumor tissues to understand the tumor microenvironment, explore biological determinants of sensitivity/resistance to immunotherapy, and potential for use as a clinical biomarker.

10:30 Discovery and Integration of Omic, Immune Profiling, and Imaging Biomarkers for Cancer Immunotherapy Development

Xingfeng Bao, Ph.D., Senior Principal Scientist & Head, Immuno-Oncology, Andover Innovative Medicine Institute, Eisai

Because cancer immunotherapies modulate tumor progression through the dynamic and systemic human immune system, biomarker research for novel Immuno-oncology (IO) agents pose quite different challenges compared with those for cancer cell-targeting agents. Here, we present a case study of biomarker discovery and application in a Phase I clinical study of a novel immunomodulator by integrating Omic, immune profiling and imaging data.

11:00 Expression Profiling and Immunohistochemistry to Identify Cancer Immune Landscapes

Darrell R. Borger, Ph.D., Director, Biomarker Laboratory, Massachusetts General Hospital Cancer Center

Immune checkpoint blockade has provided a pivotal advancement in cancer therapy. The ability to rationally direct the use of combination immune modulation or identify appropriate neoadjuvant/adjuvant therapies requires a biomarker strategy. This talk will discuss ongoing efforts to combine multiplexed molecular approaches with histological approaches to further advance the application and advancement of cancer immunotherapy.

11:30 Sponsored Presentation (Opportunity Available)

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

12:30 Session Break

IMMUNE MONITORING: BIOMARKERS OF RESPONSE TO IMMUNOTHERAPY

1:25 Chairperson’s Remarks

Sam Hanash, M.D., Ph.D., McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center

1:30 Cancer Immunotherapy Trials Network (CITN): Immune Monitoring Analysis of Multicenter Trials

Steven Fling, Ph.D., Staff Scientist, Vaccine & Infectious Disease, Fred Hutchinson Cancer Research Center; Director, Cancer Immunotherapy Trials Network Immune Monitoring Laboratory

The CITN Central Lab provides three areas of expertise essential to immune monitoring of multi-center immunotherapy trials: i) standardized specimen collection protocols ensuring integrity for multiple specimen types, ii) validated correlative assays and centralized specimen and data access to accelerate collaborative, data-driven trial design, iii) scientific guidance to support new protocols for iterative immunotherapy clinical initiatives. In-depth correlative immune monitoring results from two CITN clinical trials will be discussed.

2:00 Biomarkers for Cancer Immunotherapy Selection and Monitoring: Derived from Tissue, Blood, and Other Biospecimens

Glen J. Weiss, M.D., MBA, Director of Clinical Research and Phase I & II Clinical Trials at Cancer Treatment Centers of America, Goodyear, AZ

Recently, a number of new immunotherapies are available for clinical use for treating advanced cancer. A small portion of patients treated with monoclonal antibody immunotherapy do experience an impressive durable response. How are these therapies selected and efficacy monitored? This lecture will highlight some of the current data on biomarkers being used and evaluated for treatment selection and monitoring.

2:30 Profiling B Cell Subtypes and Autoantibodies for Immune Monitoring

Sam Hanash, M.D., Ph.D., McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center

There is increasing evidence supporting a role for B cells in tumor immunology. The presence of tumor-infiltrating B lymphocytes has been linked to a favorable clinical outcome in many types of cancers. However, B cells represent a heterogeneous population with functionally distinct subsets, and the balance among subtypes impacts tumor development. Recent findings related to B cells and to the immune response in cancer will be presented.

3:00 Refreshment Break

IMMUNOSEQUENCING AND MUTATIONAL LOAD: GENOMIC BIOMARKERS FOR IMMUNOTHERAPY PATIENT SELECTION

3:30 Immunotherapy: What’s Genes Got to Do with It?

Timothy Chan, M.D., Ph.D., Physician, Scientist, Memorial Sloan Kettering Cancer Center

Immune checkpoint blockade agents have helped improve clinical outcomes for cancer patients. It has become increasingly evident that the mutational landscape of tumors helps determine sensitivity and resistance to these agents. We will discuss the data underlying these conclusions and provide an update on the use of genetic markers for immunotherapy response.

4:00 Applying Next-Generation Sequencing to Assess Immune-Mediated Drug Hypersensitivity

Masahide Yano, Ph.D., Research Scientist, Center for Drug Evaluation and Research, FDA

Drug hypersensitivity remains a major clinical problem especially due to its unpredictable outcome in preclinical standard toxicity tests, which often causes patients’ morbidity. A goal of this study is to understand immunological mechanisms that underlie severe adverse drug reactions. To achieve this, we employed next-generation sequencing technology to identify a defined repertoire of CD8+ T cell receptors that recognize complexes of HLA/peptide/drug, and investigated their biological functions.

4:30 Development of Neoantigen Biomarkers–Are We There Yet?

Saumya Pant, Ph.D., Associate Research Director, The Biocon Bristol-Myers Squibb Research & Development Center (BBRC), Bangalore, India

Neoantigen biomarkers have gained prominence in the age of genomics-driven personalized immuno-oncology therapies. This talk will discuss the current state of the field in the aspects of approaches and technologies utilized. The talk will close with a discussion of strategies of developing rigor for neoantigen BMx development and aspects that confound the assessment of neoantigen signatures.

5:00 End of Day

TUESDAY, AUGUST 29

7:00 am Registration

7:25 Breakout Discussion Groups with Continental Breakfast

PROFILING THE TUMOR MICROENVIRONMENT AND IMMUNE CELL INFILTRATION

8:25 Chairperson’s Opening Remarks

Theresa Whiteside, Ph.D., Professor, Pathology, Immunology & Otolaryngology, University of Pittsburgh School of Medicine

8:30 Density, Distribution and Composition of Immune Infiltrates Correlate with Survival in Merkel Cell Carcinoma

Michael T. Tetzlaff, M.D., Ph.D., Assistant Professor, Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center

The efficacy of immune checkpoint blockade in anti-cancer therapy underscores the importance of immune infiltrates and their relationship to prognosis and therapeutic response. We applied automated image analyses to quantify the density and distribution of immune cells in Merkel cell carcinoma and confirm an association between patient survival and the density of T-cells at the tumor periphery. These findings establish a robust biomarker to facilitate risk stratification and a paradigm to interrogate immune infiltrates in cancer.

9:00 Major Histocompatibility Class II on Tumor Cells: Regulation, Functionality, and Predictive Role in PD-1/L1-Targeted Therapy Outcomes

Justin Balko, Pharm.D., Ph.D., Assistant Professor, Medicine & Cancer Biology, Vanderbilt University School of Medicine; Leader of Molecular Oncology, Center for Cancer-Targeted Therapies, Vanderbilt Ingram Cancer Center

Antigen presentation is a key step in the generation of anti-tumor immunity. Although most normal cells express major histocompatibility class I (MHC-I) and present cellular antigens to CD8+ T lymphocytes, some solid tumors sporadically express MHC-II which is normally restricted to professional antigen presenting cells. The cellular pathways driving this phenomenon, the functionality of MHC-II on tumor cells, and their role in marking tumors responsive to PD-1-targeted immunotherapy will be discussed.

9:30 Antigen-Presenting Tumor B Cells Impact the Phenotype of CD4 Tumor Infiltrating T Cells in Lung Cancer Patients

Tullia Bruno, Ph.D., Research Assistant Professor, Immunology, University of Pittsburgh

The focus of immunotherapy has been on CD8 and CD4 tumor infiltrating lymphocytes (TILs); however, tumor infiltrating B cells (TIL-Bs) are understudied with no focus on their role as antigen presenting cells. We hypothesize that TIL-Bs help generate potent, long-term immune responses against cancer by presenting tumor antigens to CD4 TILs.

9:45 Quantifying Non-Self in Cancer

Benjamin Greenbaum, Ph.D., Assistant Professor, Medicine, Oncological Sciences, and Pathology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai

The immunological properties of a tumor evolve as the tumor evolves, engaging the immune system in ways that create both positive and negative advantages for a tumor. During this process, mutations and epigenetics cause the presentation of molecules that are recognized as non-self. Moreover, the nature of immune engagement changes under immunotherapy, altering the nature of these immune interactions and their fitness effects on a tumor. In that sense, tumor immunology is an emergent process, whose understanding requires approaches from fields such as physics and evolutionary modeling to capture the nature of tumor-immune interactions and their therapeutic consequences. We use a set of mathematical approaches and bioinformatics analysis to quantify molecules that appear during tumorigenesis that are detected as non-self by the innate and adaptive immune system, and their effect on the tumor microenvironment and immunotherapy. In doing so, we hope to understand the role of the immune system in cancer in a manner that informs both current and future therapies.

10:00 Sponsored Presentation (Opportunity Available)

10:30 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

LIQUID BIOPSY FOR IMMUNO-ONCOLOGY

11:15 Evaluating the Clinical Utility of Circulating Tumor Cells to Predict Response to Checkpoint Immune Therapy

Terence Friedlander, M.D., Associate Clinical Professor, Hematology/Oncology, University of California, San Francisco

Checkpoint immunotherapies including those targeting PD-1/PD-L1 have demonstrated clinical activity across a number of tumor types. While immunohistochemical staining for PD-1 and PD-L1 in tissue biopsies is modestly associated with response in some cancer types, better predictive biomarkers are needed. Analyzing circulating tumor cells and cell-free DNA may help fill this niche. This talk will review the current literature and discuss options for the future.


11:45 KEYNOTE PRESENTATION: Tumor-Derived Exosomes as Potential Biomarkers of Cancer Progression and Immune Dysfunction in Cancer

Theresa Whiteside, Ph.D., Professor, Pathology, Immunology & Otolaryngology, University of Pittsburgh School of Medicine

We present evidence that the molecular cargo of plasma-derived exosomes and their effects on immune cell subsets correlate with the disease activity and tumor stage in patients with head neck cancer (HNC). Also, in patients with acute myeloid leukemia (AML), plasma exosomes carrying TGF-β induce down-regulation of NK cell activity, and the exosome cargo and their suppressive activity correlate with response of patients to chemotherapy and with leukemia relapse. The data suggest that plasma-derived exosomes could be useful in the future as non-invasive biomarkers of immune dysfunction in cancer and thus of disease progression and outcome.

12:15 pm Close of Quantitative Immune Profiling and Immune Monitoring


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