AACR Cancer Evolution Seminar Series – first 2022 event

When: Thursday, January 6, 2022, from 11:00 AM – 13:00 PM (ET)

Where: Zoom (Open to All & Free to Attend – Zoom Details Below)

 

Join Dr. Giulia C. Kennedy, Veracyte’s Chief Scientific and Medical Officer, as she moderates the kick-off session for the AACR’s 2022 Cancer Evolution Seminar Series on Thursday, January 6, 2022. Dr. Kennedy will facilitate the seminar among three guest speakers, which will conclude with a scientific group discussion.

 

SEMINAR PARTICIPANTS  

MODERATOR 

Giulia C. Kennedy, PhD

Chief Scientific Officer and Chief Medical Officer, Veracyte, Inc.

Giulia joined Veracyte in 2008 as a member of the founding team, Dr. Kennedy has overseen the development and commercialization of eight genomic tests that changed the standard of patient care, with two more on track for a 2021 launch. Through Dr. Kennedy’s scientific, clinical and medical leadership, Veracyte continually pushes the boundaries of what is possible by using big data and machine learning to develop tests that answer critical clinical questions. Prior to Veracyte, Dr. Kennedy was Senior Director of Genomics Collaborations at Affymetrix, Inc. and led the transition of a novel microarray-based genotyping method from early research through product development and successful commercialization.  Previously, Dr. Kennedy was a scientific leader for the colon cancer and breast cancer gene discovery efforts at Chiron Corporation. Before that, she was a scientist at Millennium Pharmaceuticals, where she implemented genetic approaches to study diabetes.

In addition to serving as a member of the Board of Directors at Astarte Medical since 2018, she is an advisor for the UCSF Catalyst program, a translational accelerator focused on advancing discoveries with clinical impact and commercial potential and is on the Medical Advisory Board of InterVenn, a diagnostic company commercializing tests for ovarian, pancreatic and other cancers. In 2020 Dr. Kennedy was named one of the Bay Area’s 100 Most Influential Women in Business by the San Francisco Business Times.

Dr. Kennedy holds a Ph.D. degree in Biochemistry and completed postdoctoral training at the University of California at San Francisco in the Biochemistry Department and Hormone Research Institute. Dr. Kennedy has published more than 70 articles in peer-reviewed scientific journals and is a co-inventor on more than 30 patents.

 

SPEAKERS

Jérôme Galon, PhD,

Director of Research, French National Institute of the Health and Medical Research (INSERM), Chief of Laboratory of Integrative Cancer Immunology, Cordeliers Research Center, Paris, France

Dr. Jérôme Galon is Director of Research at INSERM (French NIH), and Head of the laboratory of Integrative Cancer Immunology, in Paris, France. Dr. Galon was trained as an immunologist at the Pasteur Institute and at the Curie Institute (Paris, France). He holds a Ph.D. degree in Immunology (Jussieu University, Paris, France, 1996). Between 1997 and 2001 he worked at the NIH (National Institute of Health, Bethesda, USA). Since his full-tenured position at INSERM in 2001, he directs interdisciplinary research programs on tumor-Immunology. He is associate Director and co-founder of European Academy of Tumor Immunology (EATI), was board Director of the Society for Immunotherapy of Cancer (SITC). His work on the comprehensive analysis of the tumor-microenvironment and the role of T-cells in human cancer led to the demonstration of the importance of adaptive pre-existing immunity in human cancer, and the concept of cancer immune-contexture. He pioneered the Immunoscore. He is the co-founder of HalioDx company a Veracyte company and Chief Scientific Officer Immuno-oncology. His contributions have been recognized with numerous awards, including the William B. Coley Award, an international prize which honors the best scientists in the fundamental and cancer immunology, and Award from the National Academy of Science, Award from the National Academy of Medicine. He won the prestigious European Inventor Award in Research category in 2019, the Jeantet-Collen Prize in 2020, and is finalist for the Galien Prize 2021.

Title: Immune Selection Model of Cancer Evolution

Abstract: We have previously shown that tumors from human colorectal cancer with a high-density of infiltrating memory and effector-memory T-cells are less likely to disseminate to lympho-vascular and perineural structures and to regional lymph-nodes. We also demonstrated the critical tumor-microenvironment parameters determining the dissemination to distant metastasis. We found that the combination of immune parameters associating the nature, the density, the functional immune orientation and the location of immune cells within the tumor was essential to accurately define the impact of the local host-immune reaction on patients’ prognosis. We defined these parameters as the “immune contexture”. We characterized the immune landscape within human tumors, and showed the importance of several adaptive immune cells. Analyses revealed a large inter- and intra-metastatic tumor cell and immune heterogeneity. We further demonstrated the significant role of Immunoscore and immunoediting in affecting metastatic clonal dissemination. We hence proposed a “parallel immune selection model” of tumor evolution incorporating the effects of the immune system in shaping and driving metastatic spread. We proposed a continuum of cancer immunosurveillance from pre-cancer to metastasis, and novel concepts underpinning tumor evolution at the pre-cancerous stages will be advocated.

 

Klaus Lindpaintner, MD, MPH, FACP

Chief Scientific and Medical Officer at InterVenn Biosciences

Dr. Lindpaintner previously held senior positions at Pfizer as Sr. VP and Global Head, Human Genetics and Computational Biomedicine, at Hoffman-La Roche, as Sr. VP and Director, Roche Center for Medical Genomics, as CSO at Thermo-Fisher-Scientific; and on the faculty of Harvard Medical School.

Klaus has co-authored some 250 scientific papers, and holds honorary and adjunct professorships at several academic institutions. He serves on numerous boards, working groups, and advisory panels for trade organizations, regulatory authorities, and non-governmental organizations on issues related to the successful implementation and leverage of novel technologies in health care.  Klaus graduated from Innsbruck University Medical School with a degree in medicine, and from Harvard University with a degree in public health. He pursued post-graduate training and specialization in internal medicine, cardiology, and clinical and molecular genetics in the US and Germany and is a Diplomate of the Boards in these specialties.

Title: High Resolution Glycoproteomics as a Source of Liquid Biopsy Biomarker

Abstract: InterVenn biosciences has developed a novel technology platform consisting of ultra-high pressure liquid chromatography/triple quadrupole mass spectrometry coupled to an artificial intelligence/recurrent neural network-supported data processing engine that has allowed to decrease chromatogram analysis time by 4-5 orders of magnitude, thus allowing the application of high-resolution interrogation of the plasma proteome at scale, making it applicable to clinical studies. Using this platform, we have been able to demonstrate that changes in the glycoprotein profile of abundant plasma proteins, such as immunoglobulins, complement factors, and acute phase reactants are commonly encountered in a number of clinical disorders, in particular oncological disorders, and represent useful, high accuracy biomarkers both for disease characterization as well as for therapy response prediction and selection. Examples of the performance of the platform for the non-invasive differentiation of pelvic tumors into benign and malignant disease, and for the prediction of response to immune-checkpoint inhibitor therapy will be presented.

 

Wendy J. Fantl, PhD

Assistant Professor in the Department of Urology with a courtesy appointment in ObGyn at Stanford University Medical School.

Dr. Fantl is an Associate Faculty Member of the Canary Center at Stanford for Early Cancer Detection and a Member of the UCSF Center for BRCA research. She obtained her PhD at Rockefeller University in protein Biochemistry and completed her post-doctoral studies at UCSF where she made seminal discoveries in PDGF-mediated signaling pathways. Prior to Stanford, Dr Fantl spent over a decade in the Biotech arena at Chiron and Nodality. At Stanford, she leads a laboratory program that studies ovarian and kidney cancer to address their areas of unmet clinical need. Specifically, her lab addresses two key questions related to drug resistance and immunotherapy. Firstly, why do most ovarian cancer patients initially respond to chemotherapy but eventually experience relapse and chemotherapy-resistant disease? The second question asks why some malignancies respond to immunotherapy whereas others do not. To fulfill these goals, she applies multi-parametric single-cell proteomic technologies (mass cytometry aka Cytometry by Time-Of-Flight (CyTOF) and CODetection by indEXing (CODEX) imaging) combined with specialized computational approaches for analyzing single-cell datasets. These technologies reveal cell heterogeneity identifying minority cell subpopulations of interest, such as those with roles in metastasis and therapeutic resistance, that would elude bulk analyses. Dr Fantl is deeply committed to translating her findings in the lab to helping patients.

Title: High-Grade Serous Ovarian Tumor Cells Modulate NK Cell Function to Create an Immune-Tolerant Microenvironment

Abstract: Tubo-ovarian high-grade serous carcinoma (HGSC) is unresponsive to immune checkpoint blockade despite significant frequencies of exhausted T cells. Here we apply mass cytometry (aka CyTOF) and uncover decidual-like (dl)-NK cell subpopulations (CD56+CD9+CXCR3+KIR+CD3-CD16-) in newly diagnosed HGSC samples that correlate with both tumor and transitioning epithelial-mesenchymal cell abundance. Decidual NK cells are critical in the first trimester of pregnancy by conferring immune tolerance to the hemi-allogeneic fetus.

To gain insight into the immunosuppressive mechanisms of HGSC intra-tumoral dl-NK cells, we show different combinatorial expression patterns of ligands for activating and inhibitory NK receptors within three HGSC tumor compartments; epithelial (E), transitioning epithelial-mesenchymal (EV) and mesenchymal (vimentin-expressing (V)), with a more inhibitory ligand phenotype in V cells. In cocultures, NK cells acquire CD9 from HGSC tumor cells by trogocytosis resulting in reduced anti-tumor cytokine production and cytotoxicity. Cytotoxicity in these cocultures is restored with a CD9 blocking antibody or CD9 CRISPR knockout thereby identifying previously unrecognized mechanisms of immune suppression in HGSC. CD9 is widely expressed in HGSC tumors and so represents an important new therapeutic target with immediate relevance for NK immunotherapy.

 

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