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 Immune Profiling in Cancer meeting will cover 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
Wednesday, May 3
12:00 pm Conference Registration
12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:30 Dessert Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Opening Remarks
Robert Iannone, M.D., Senior Vice President & Head, Immuno-Oncology, Global Medicines Development, AstraZeneca
2:05 Immunophenotyping to Differentiate Responder and Non-Responder Patients in Cancer Immunotherapy
George Poste, D.V.M., Ph.D., Chief Scientist, Complex Adaptive Systems, Arizona State University
The clinical benefits of immune checkpoint inhibitors in a variety of malignancies are unprecedented. Unfortunately, the level of positive therapeutic response is not consistent across different tumor classes and even in responsive tumor lineages non-responders still dominate. The need for comprehensive immunophenotyping to identify the mechanisms underlying these differential reponses and better predict responder patients is an urgent clinical and economic imperative.
2:30 Rational Combinations with PD-L1 Antagonists
Robert Iannone, M.D., Senior Vice President & Head, Immuno-Oncology, Global Medicines Development, AstraZeneca
2:55 Non-Clinical Approaches to Predict Single Agent vs. Combination Value and Clinical Development Strategies for Emerging Cancer Immunotherapies
James Smothers, Ph.D., Senior Director & Head, Discovery, Immuno-Oncology & Combinations DPU, GlaxoSmithKline
A rapidly growing number of immunotherapy treatments for cancer have entered clinical trials and are being evaluated for both single agent and combination therapeutic value. Currently approved or mature Phase III evaluations of immuno-oncology treatments are largely limited to strategies that employ either autologous T-cell treatments or use of monoclonal antibodies (mAbs) to block T-cell checkpoints of either activation or exhaustion. Other modalities being explored in late phase preclinical and early clinical development include agonistic mAbs that modulate healthy immune cell populations, small molecule chemistries to inhibit or drive enzymatic function, and other emerging or reconsidered approaches to experimental medicine design. Non-clinical research studies historically support preclinical development and regulatory submission satisfaction and provide critical support of early clinical development hypotheses and clinical trial design including managing expectations of single agent efficacy or setting strategic vision for combination value through biology synergies. Moreover, following early clinical development milestones, an experimental medicine requires ongoing translational review of the clinical readouts beyond efficacy which in turn requires additional non-clinical analyses and experimental execution to drive results-based decision making and data-informed design of late stage clinical trials in anticipation and hope of drug approvals. Examples of non-clinical studies to support all of these activities will be reviewed including choice of experimental models and design.
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:10 Chairperson’s Opening Remarks
Christopher R. Heery, M.D., CMO, Bavarian Nordic
4:15 CARTography: Mass Cytometry-Based Approach to Multi-Dimensional Phenotyping of Anti-CD19 CART Cells
Piotr Pierog, Ph.D., Associate Director, Oncology Precision Medicine, Novartis
We have generated highly multiplexed CyTOF data on cellular therapy products. Through data analysis and mining approaches, we have successfully characterized T cell subset frequencies and uncovered their corresponding phenotypes. Deep characterization of immune cells through mass cytometry approach provides a powerful tool for decoding the complexity of immune cell compartments and cellular biomarker discovery. Specific T cell phenotypes, or associated map locations, can then be used to correlate product phenotype with cell manufacturing process, patient outcomes and/or safety profiles.
4:40 SeroTag: Longitudinal Autoantibody Profiling of Clinical Trials in Cancer Vaccination and Checkpoint Inhibition
Peter Schulz-Knappe, Ph.D., CSO, Protagen AG
We performed Proof-of-Concept studies together with NCI (Bethesda, USA) and NCT (Heidelberg, Germany) in several Immuno-Oncology trials. Are autoantibodies biomarkers which show promise to measure response to immuno-therapy and to monitor immune-related adverse events (irAEs) before and during cancer treatment? Concept, Strategy and PoC results will be presented and discussed.
4:55 Peripheral Immune Correlates of Therapeutic Cancer Vaccine Clinical Trials
Christopher R. Heery, M.D., CMO, Bavarian Nordic
Dr. Heery will discuss the use of a flow-based assay to identify specific immune cell subsets from PBMC in a retrospective analysis of two clinical trials. Immune cell subset populations correlated with clinical impact of immunotherapy in combination with cytotoxic agents, but those same populations did not predict effect of cytotoxic therapy alone. Dr. Heery will discuss how this can be used in future trials for therapeutic development.
5:20 Tumor Immunophenotyping of Exhausted T Cells and Response to PD-1 Therapy
Adil Daud, M.D., Professor, Hematology/Oncology, University of California, San Francisco; Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center
5:45 Short Course and ThinkTank Registration
6:15 - 9:15 Dinner Executive ThinkTank*
SC6: Complementary Diagnostics
6:15 - 9:15 Dinner Short Course*
SC7: Immune Monitoring in Cancer
*Separate registration required
Thursday, May 4
8:30 am Morning Coffee
9:00 Chairperson’s Remarks
Lance D. Miller, Ph.D., Associate Professor, Cancer Biology, Wake Forest University
9:05 Deep Sequencing of T Cell Receptor DNA as a Biomarker of Clonally Expanded TILs in Breast Cancer after Immunotherapy
David B. Page, M.D., Medical Oncology, Providence Cancer Center
In early-stage breast cancer (ESBC), the degree of tumor-infiltrating lymphocytes (TIL) predicts response to chemotherapy and overall survival. Immune checkpoint antibody (ipilimumab, anti-CTLA-4) plus tumor cryoablation can induce TILs and improve survival in mice, and was recently evaluated as a pre-operative strategy in ESBC. We will describe how T cell receptor (TCR) DNA sequencing can be used in the context of immunotherapy to quantify TILs and to indirectly assess for antigen-reactive T cell clonal expansions.
9:30 Immunogenomics and Single Cell Omics for Cancer Precision Medicine
Olivier Elemento, Ph.D., Associate Professor & Associate Director, Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine
I will present my group’s work on the development and implementation of a clinical grade (CLIA) whole-exome sequencing based genomic test for precision cancer medicine and immunotherapy. A novel analytical pipeline that analyzes genomic profiles to unravel the immune landscape of tumors and integrates multi-omics features using machine learning to predict immunotherapy response will be described. Finally, high-throughput single cell genomics approaches to dissect the tumor microenvironment and unravel immune repertoires at the single cell resolution will be presented.
9:55 Comprehensive Immune Profiling for Response to Checkpoint Inhibitor Therapy: A Multi-Institutional Retrospective Study
Carl Morrison, M.D., D.V.M., President, Founder & CSO, OmniSeq Precision Medicine
Mutation burden, microsatellite instability, T cell receptor signaling, tumor infiltrating lymphocytes, PD-L1 IHC, and PD-L1/2 copy number have all been identified as candidate biomarkers for response to checkpoint inhibitors (CPI). We have developed a high-throughput CLIA NYS-CLEP approved assay to measure all of these variables in a single assay. A multi-institutional retrospective study of patients with prior CPI therapy and follow-up by RECIST criteria was performed using this approach to predict response.
10:25 Networking Coffee Break
10:45 Genomic Correlates of Immune Infiltration in Colorectal Cancer
Marios Giannakis, M.D., Ph.D., Medical Oncologist & Clinical Investigator, Dana-Farber Gastrointestinal Cancer Treatment Center; Researcher, Broad Institute of MIT and Harvard
Large-scale genomic characterization of tumors with clinicopathologic annotations can yield insights into cancer pathogenesis and immunobiology. We performed whole-exome sequencing of 619 colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, and survival data. We found that a higher tumor neoantigen load was associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs), memory T cells and CRC-specific survival. We also found positive selection of antigen-processing machinery mutations in TIL-rich tumors.
11:10 The Function and Specificity of T Cells in Colorectal Cancer
Arnold Han, M.D., Ph.D., Assistant Professor, Medicine, Digestive and Liver Diseases and Microbiology & Immunology, Columbia University
We have begun to systematically study the function and antigen specificity of TILs in colorectal cancer. Through single-cell approaches, we have characterized the TCR repertoire and diverse pro-inflammatory and regulatory phenotypes of colorectal tumor-infiltrating T cells. We are also working to study the TCR specificity of TILs through novel approaches.
11:35 B- and T-Cell Immune Repertoire Characterization by Anchored Multiplex PCR and Next-Generation Sequencing
Laura Griffin, Ph.D., Scientific Liaison, ArcherDX
The immune repertoire (IR) provides a means to monitor adaptive immune responses to disease, vaccination and therapeutic interventions. NGS-based IR characterization usually requires large primer panels to capture its extensive combinatorial diversity and a complex system of synthetic controls to account for differential amplification efficiency across segment combinations. Here, we discuss how Anchored Multiplex PCR (AMP™) enables NGS-based IR characterization with a minimal set of unidirectional gene-specific primers and molecular barcodes that reduce amplification bias.
12:05 pm Genetic Biomarkers of Immune Responsiveness and Breast Cancer Immunogenicity
Lance D. Miller, Ph.D., Associate Professor, Cancer Biology, Wake Forest University
Immunotherapies are advancing in the clinic, but the ability to predict patient benefit remains a major challenge. Central to this problem is a lack of understanding of how tumor-intrinsic factors interact with the host immune system to influence patient outcomes. In this presentation, I will discuss genomic and bioinformatics strategies we’ve used to uncover cellular and genomic rules that appear to govern the immunogenic potential of breast and other cancers.
12:25 Session Break
12:35 Luncheon Presentation: A Novel Phenotypic Platform for Predicting Tumor Response in Drug Development
Mark Paris, Ph.D., Technical Liaison, Mitra Biotech
1:40 Chairperson’s Opening Remarks
Sam Hanash, M.D., Ph.D., McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center
1:45 Density, Distribution and Composition of Immune Infiltrates Correlate with Survival in Merkel Cell Carcinoma
Michael T. Tetzlaff, M.D., Ph.D., Associate Professor, Pathology and Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma with frequent metastasis and death. Robust biomarkers predictive of clinical outcome are lacking, and few effective agents exist for MCC therapy. The emergence of immune checkpoint blockade therapies that mobilize antitumoral immunity provides a strong rationale to define the density, distribution, and composition of immune infiltrates in MCC to determine whether any of these impact clinical outcome and thus, could be reasonably leveraged in treatment strategies. We performed immune profiling for CD3, CD8, PD-1, and PD-L1 in a series of MCC with carefully annotated clinical outcomes and used automated image analysis to precisely quantify immune cell density at distinct tumor locations. We confirm a significant association between patient survival and the density of CD3+ and CD8+ T cells specifically at the tumor-stroma interface. Together, our findings provide a robust biomarker to facilitate risk stratification and prognosis in MCC and additional rationale to deploy immune checkpoint inhibitors in MCC treatment.
2:10 Defining Dynamic Changes in the Tumor Microenvironment with Tumor Development and Progression
Sam Hanash, M.D., Ph.D., McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center
While genomic alterations are driving forces in tumor development, the tumor microenvironment is critical to tumor development and metastasis. Molecular profiling including proteomics and metabolomics are contributing to defining the constituents of the microenvironment and their source, modifications, interactions and turnover, and how these features relate to tumor development and progression.
2:35 The Impact of STAT3 on Tumor Immunological Environment
Hua Yu, Ph.D., Professor & Co-Chair, Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center
A crucial role of STAT3 in promoting cancer has been established. STAT3 signaling within tumor cells and tumor-associated immune cells also induces immunosuppression. Our recent studies including metabolic profiling highlight the importance of STAT3 in regulating lipid metabolism in tumor cells and cancer stem cells. Extensive work has also demonstrated the significance of STAT3-regulated metabolism in suppressing tumor T cells. We plan to perform lipid metabolic profiling of tumor-associated T cells.
3:00 Close of Conference