Licia Rivoltini, MD Unit of Immunotherapy of Human Tumors
|
|
- Emmeline Butler
- 6 years ago
- Views:
Transcription
1 Licia Rivoltini, MD Unit of Immunotherapy of Human Tumors
2 The complex network of anti-tumor immunity Innate immunity First line defense Tumor cell Adaptive immunity Specificity & memory Kidd et al., Nature Biotech 2015
3 CD8+ T cells: key players in tumor rejection B cell depleted CD8+ T cell depleted Adoptive immune cell transfer CD8+ T cell depleted CD8+ T cells B cell depleted CD4+ T cells NK cells B cells Fox et al., J clin Invest 2015
4 CD8+ T cells: clonal expansion and immune memory Tumor (?) Expansion of tumor-specific effector cells (optimal priming, adequate cytokines and growth factors contexture) Induction of immune memory (central and effector memory cells for long-term protection)
5 CD8+ T cells: selective and potent tumor killers TCR Cytotoxic granules (perforin, granzyme B) HLA/Antigen complex Cell apoptosis FasL Fas Immunological synapse Activated CD8+ cytotoxic T cells (CTL) Tumor cell
6 Homing of cytotoxic CD8+ T cells to tumor site Tumor killing A Initial tumor elimination by NK cells T cell exhaustion Tumor antigens A A A A A Lymph node A A Dendritic cells Process and present Ag to specific T cells Clonal expansion of cytotoxic antitumor CD8+ T cells generation of memory cells Peripheral blood
7 Immune checkpoints Stop of proliferation Reduced glucose consumption Inhibition of cytotoxicity and cytokine release Blocking of antibody production In a reversible fashion
8 Immune checkpoint (CTLA4, PD1) anti-pdl-1 Nguyen et al., Nature Rev Immunol 2015
9 Immune checkpoint (CTLA4, PD1) pakt/pi3k anti-pdl-1 Nguyen et al., Nature Rev Immunol 2015
10 Predictive factors of response? 30-40% 15% Patrick A. Ott et al. Clin Cancer Res 2013;19:
11 T cell Tumor cell
12 T cell Neo antigen level of tumor antigens Tumor cell
13 T cell level of T cell infiltrate level of PD-1 expression in T cells PD-1 Neo antigen level of tumor antigens Tumor cell
14 T cell level of T cell infiltrate level of PD-1 expression in T cells level of PD-L1 expression in tumor cells (and stroma) PD-1 PDL-1 Neo antigen level of tumor antigens Tumor cell
15 Tissu antigens Muc1,MART-1, PSMA..) Unique mutated antigens or NEO-ANTIGENS (non-synonimous mutations due to genetic instability)
16 Tissu antigens Muc1,MART-1, PSMA..) Unique mutated antigens or NEO-ANTIGENS (non-synonimous mutations due to genetic instability) NSCLC Melanoma High mutations High mutations Low mutations Low mutations Lysis of: autologous tumor, common tumors same histotye, common tumor different histotype Rizvi et al. Science, 2015 McGranahan et a., Science 2016
17 Tissu antigens Muc1,MART-1, PSMA..) Unique mutated antigens or NEO-ANTIGENS (non-synonimous mutations due to genetic instability) NSCLC Melanoma High mutations High mutations Low mutations Low mutations Lysis of: autologous tumor, common tumors same histotye, common tumor different histotype Rizvi et al. Science, 2015 McGranahan et a., Science 2016 Mohini Rajasagi et al. Blood 2014;124:
18 DNA damage response gene mutations, mutational load, and sensitivity to chemotherapy plus immune checkpoint blockade in urothelial cancer DDR mutant UC is associated with Higher mutational load Higher CD8+ T cell infiltrate Potentially higher sensitivity to CT+ICI
19 DNA damage response gene mutations, mutational load, and sensitivity to chemotherapy plus immune checkpoint blockade in urothelial cancer DDR mutant UC is associated with Higher mutational load Higher CD8+ T cell infiltrate Potentially higher sensitivity to CT+ICI small cell neuroendocrine carcinoma of the urinary bladder. Pal et al., Foundation Medicine Boston
20 T cell level of T cell infiltrate level of PD-1 expression in T cells level of PD-L1 expression in tumor cells (and stroma) PD-1 PDL-1 Neo antigen level of tumor antigens Tumor cell
21
22 ADAPTIVE IMMUNE RESPONSE (activated CD8+ T cells) PD-L1 in tumor cells Inducible expression due to local inflammation cytokines and chemokines IFN produced by T cells
23 PD-L1 in LN, blood and BM ADAPTIVE IMMUNE RESPONSE (activated CD8+ T cells) PD-L1 in tumor infiltrating stroma (myeloid) cells Inducible expression due to local inflammation cytokines and chemokines IFN produced by T cells PD-L1 in tumor cells
24 PD-L1 in LN, blood and BM ADAPTIVE IMMUNE RESPONSE (activated CD8+ T cells) Surrogated by CD80 PD-L1 in tumor infiltrating stroma (myeloid) cells Inducible expression due to local inflammation cytokines and chemokines IFN produced by T cells Constitutive expression due to oncogenic pathways HIF1a-hypoxia VHL EGFR activation AP-1 signaling PTEN loss PI3K/AKT/mTOR PD-L1 in tumor cells
25 Impact of immune checkpoint protein expression in tumor cells nd tumor infiltrating CD8+ T cells on clinical benefit from PD-1 blockade in mrcc Expression of either PDL-1 or PD-L2 on tumor cells and low infiltration by T cells expressing multiple IC are associated with better response to ICI
26 hot hot PD-1 blockade HOT TUMORS COLD TUMORS cold Lizotte et al, J Clin Invest 2016 Daud et al, J Clin Invest 2016
27 T cell LOW level of T cell infiltrate LOW level of PD-1 in T cells LOW level of PD-L1 in tumor cells (and stroma) LOW level of tumor antigens (neo-antigens) Tumor cell
28 T cell Immunosuppressive immune components LOW level of T cell infiltrate Myeloid-derived suppressor cells LOW level of PD-1 in T cells LOW level of PD-L1 in tumor cells (and stroma) Tumor associated macrophages Regulatory T cells LOW level of tumor antigens (neo-antigens) Tumor cell
29 Myeloid derived suppressor cells Granulocytic MDSC (activated neutrophil-like cells) CD33+CD15+CD11b+LDG STAT ROS Monocytic MDSC (immature monocyte-like cells) CD33+CD11b+CD14+HLA-DRneg Arginase-1 TGFb inos PD-L1
30 Myeloid derived suppressor cells Granulocytic MDSC (activated neutrophil-like cells) CD33+CD15+CD11b+LDG STAT Monocytic MDSC (immature monocyte-like cells) CD33+CD11b+CD14+HLA-DRneg ROS Local effect Arginase-1 TGFb PD-L1 inos Systemic effect Immune suppression Stroma remodelling Neoangiogenesis Mesenchymal transition Pre-metastatic niche Bone metastases
31 An immunosuppressive protumoral microenviroment defines intrinsic resistance to anti-pd-1 therapy Genes involved in mesenchymal transition, cell adhesion, extracellular matrix remodeling, angiogenesis, wound healing and myeloid derived suppressor cells (IPRES signature) Hugo et al., Cell 2016
32 Myeloid Index Score Monocytic MDCS Rivoltini et al., manuscript in prep Sade-Feldman et al., Clin Cancer Res 2016
33 Absolute neutrophil count Myeloid Index Score Monocytic MDCS Neutrophil to lymphocyte ratio Rivoltini et al., manuscript in prep Sade-Feldman et al., Clin Cancer Res 2016 Ferrucci et al., Ann Oncol 2015
34 Neutrophil lymphocyte ratio (NLR) as a clinical biomarker predictive of outcomes with immune checkpoint inhibition therapy in genitourinary cancers
35 Evaluation of monocytic myeloid-derived suppressor cell (m-mdsc) frequency in patients with metastatic urothelial carcinoma
36 How to improve efficacy? 30-40% 15% Patrick A. Ott et al. Clin Cancer Res 2013;19:
37 Mechanisms of tumor cell death in local therapies Cryoablation Cryoablation Radiotherapy Radioembolization Chemoembolization Cryoablation Radiotherapy Radioembolization Chemoembolization Katrina F. Chu & Damian E. Dupuy Nature Rev Cancer 2014
38 (presurgery) Ablative therapy to induce local and systemic immune changes in patients with metastatic RCC Intratumor: Increase of PD1+ T cells Higher expression of immune gene signatures Blood: Decrease of Treg cells and IL-6 levels (transient window) Clinical pilot study of anti-ctla4 +/- cryoablation in mrcc patients
39 (presurgery) Ablative therapy to induce local and systemic immune changes in patients with metastatic RCC Intratumor: Increase of PD1+ T cells Higher expression of immune gene signatures Blood: Decrease of Treg cells and IL-6 levels (transient window) Clinical pilot study of anti-ctla4 +/- cryoablation in mrcc patients HCC patients treated with TARE (transarterial radio-embolization) display a window of systemic immune modulation (Rivoltini and Mazzaferro, in preparation)
40 Pembrolizumab plus low dose ipilimumab for patients with advanced renal carcinoma: phase I KEYNOTE-029 study Managble toxicity and significant activity (disease control rate 50%) Choueiri et al. Evaluation of clinical activity of IPI and NIVO in patients with NIVO-refractory metastatic urothelial cancer IPI and NIVO is active in UC patients who failed NIVO Callahan et al.
41 Pembrolizumab plus low dose ipilimumab for patients with advanced renal carcinoma: phase I KEYNOTE-029 study Managble toxicity and significant activity (disease control rate 50%) Choueiri et al. Evaluation of clinical activity of IPI and NIVO in patients with NIVO-refractory metastatic urothelial cancer IPI and NIVO is active in UC patients who failed NIVO Callahan et al. Cell transition and DNA replication Cell cycle CDK cyclins Differentiation and expansion of T cells Effector T cells NK cell function IL-12/IFNgamma response Differentiation and clonal expansion of CD8+ T cells Granzyme B/perforin lytic machinery Pei-Ling Chen et al. Cancer Discov 2016;6:
42 Distinct but synergistic effects of CTLA-4 and PD-1 blockade Lymph node Tumor lysis by innate cells (or cancer therapies) and antigen relase Antigen up-take, process and presentation by dendritic cells Priming of antigen-specific T cells by dendritic cells CTLA-4 Effect of blockade Resques dendritic cell tolerance Improves T cell priming by dendritic cells Reduces immunosuppression by Treg Increases T cell proliferation and function T cell clonal expansion and trafficking from regional lymph nodes to tumor site Tumor infiiltration by specific T cells Potentiates T cell effector functions Increases T cell proliferation Rescuses T cells from inhibition by PD-L1+ myeloid-derived suppressive cells Effect of blockade PD-1 Tumor lysis by xx tumor infiltrating T cells Tumor site
43 Outcomes of PD-1/PD-L1 responders who discontinued therapy for immune related adverse events (iraes): results of a cohort of patients with mrcc In 9 patients, long-term responses after only a median duration therapy of 5 mo (4-15). Induction of Immune memory? Im et al., Nature 2016
44 Outcomes of PD-1/PD-L1 responders who discontinued therapy for immune related adverse events (iraes): results of a cohort of patients with mrcc In 9 patients, long-term responses after only a median duration therapy of 5 mo (4-15). Induction of Immune memory? Chronic immune stimulation induces memory responses that are blocked by PD-1 a-pd-1 control Im et al., Nature 2016 Utzschneider et al., Immunity 2016
45 Impact of antibiotics on outcome in patients with mrcc treated with ICI Antibiotic therapy before or during ICI is associated with poor PFS and OS during ICI therapy (n=80)
46 Impact of antibiotics on outcome in patients with mrcc treated with ICI Antibiotic therapy before or during ICI is associated with poor PFS and OS during ICI therapy (n=80) ICI responding patients expand a microbiota cluster Transplant of the C cluster reverts ICI resistance in mice Vétizou et al,science 2015
47 To summarize o Strong scientific rational of GU tumors sensitivity to Immune checkpoint inhibitors o Immunogenic tumors (more neoantigens, more mutations, more mutational load, more infiltrating T cells, more PD-1/PDL-1, 2 expression) are more likely to respond o Myeloid-enriched tumors (microenvironmentally or systemically) are more likely to fail responding to ICI(preconditioning required?) o Combinations (ablation, multiple ICI ) should be more effective. But avoid antibiotics (?) o Potential long-term immune memory with PD-1 blockade (like with a-ctla4)
48 Thank you
49 Mutation burden as a biomarker of response to immune checkpoint in nine solid cancers: the new concept of icam icam: mutation burden threshold, a gene expression signature of a blocked immune response of robust CD8+ T cell response and up-regulation of immune checkpoints Using data from 10,745 tumors from 33 solid cancer type in TGCA, icam is expressed in Melanoma Lung cancer Colon cancer Endometrial Gastric adenocarcinoma Serous ovarian Bladder urothelial Cervical Her2+ breast cancer icam represents a clinically useful mutation burden threshold
Camillo Porta S.C. di Oncologia Medica Università degli Studi di Pavia & I.R.C.C.S. Fondazione Policlinico San Matteo di Pavia
Keynote Lecture: Immunotherapy in GU cancer: where are we, and where are we going? Camillo Porta S.C. di Oncologia Medica Università degli Studi di Pavia & I.R.C.C.S. Fondazione Policlinico San Matteo
More informationDarwinian selection and Newtonian physics wrapped up in systems biology
Darwinian selection and Newtonian physics wrapped up in systems biology Concept published in 1957* by Macfarland Burnet (1960 Nobel Laureate for the theory of induced immune tolerance, leading to solid
More informationCheckpoint Regulators Cancer Immunotherapy takes centre stage. Dr Oliver Klein Department of Medical Oncology 02 May 2015
Checkpoint Regulators Cancer Immunotherapy takes centre stage Dr Oliver Klein Department of Medical Oncology 02 May 2015 Adjuvant chemotherapy improves outcome in early breast cancer FDA approval of Imatinib
More informationImmune Checkpoints. PD Dr med. Alessandra Curioni-Fontecedro Department of Hematology and Oncology Cancer Center Zurich University Hospital Zurich
Immune Checkpoints PD Dr med. Alessandra Curioni-Fontecedro Department of Hematology and Oncology Cancer Center Zurich University Hospital Zurich Activation of T cells requires co-stimulation Science 3
More information2/16/2018. The Immune System and Cancer. Fatal Melanoma Transferred in a Donated Kidney 16 years after Melanoma Surgery
C007: Immunology of Melanoma: Mechanisms of Immune Therapies Delphine J. Lee, MD, PhD Chief and Program Director, Dermatology, Harbor UCLA Medical Center Principal Investigator, Los Angeles Biomedical
More informationTumor Microenvironment and Immune Suppression
Tumor Microenvironment and Immune Suppression Hassane M. Zarour,, MD Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Cancer Institute Hallmarks of Cancer: The Next Generation
More informationBasic Principles of Tumor Immunotherapy and Mechanisms of Tumor Immune Suppression. Bryon Johnson, PhD
Basic Principles of Tumor Immunotherapy and Mechanisms of Tumor Immune Suppression Bryon Johnson, PhD Disclosures There will be discussion about the use of products for non-fda indications in this presentation.
More informationRadiation Therapy as an Immunomodulator
Radiation Therapy as an Immunomodulator Yvonne Mowery, MD, PhD February 20, 2017 Tumor/Immune System Balance Kalbasi, JCI 2013 UNC-Duke-NC State-Wake Forest Spring 2017 2 RT Can Shift Balance Toward Elimination
More informationDeveloping Novel Immunotherapeutic Cancer Treatments for Clinical Use
Developing Novel Immunotherapeutic Cancer Treatments for Clinical Use Oncology for Scientists March 8 th, 2016 Jason Muhitch, PhD Assistant Professor Department of Urology Email: jason.muhitch@roswellpark.org
More informationI farmaci immunoterapici. Stefano Fogli UO Farmacologia Clinica e Farmacogenetica Dipartimento di Medicina Clinica e Sperimentale Università di Pisa
I farmaci immunoterapici Stefano Fogli UO Farmacologia Clinica e Farmacogenetica Dipartimento di Medicina Clinica e Sperimentale Università di Pisa History of Cancer Immunotherapy Discovery of dendritic
More informationTHE ROLE OF TARGETED THERAPY AND IMMUNOTHERAPY IN THE TREATMENT OF ADVANCED CERVIX CANCER
Gynecologic Cancer InterGroup Cervix Cancer Research Network THE ROLE OF TARGETED THERAPY AND IMMUNOTHERAPY IN THE TREATMENT OF ADVANCED CERVIX CANCER Linda Mileshkin, Medical Oncologist Peter MacCallum
More information5% of patients with genetic immunodeficiency develop a cancer during their lifetime (200x)
Immune surveillance 5% of patients with genetic immunodeficiency develop a cancer during their lifetime (200x) Transplanted patients following an immunosuppressor therapy are 80 times more likely to develop
More informationRegulation of anti-tumor immunity through migration of immune cell subsets within the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D.
Regulation of anti-tumor immunity through migration of immune cell subsets within the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D. Professor, Departments of Pathology and Medicine Program Leader,
More informationGeneral Overview of Immunology. Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center
General Overview of Immunology Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center Objectives Describe differences between innate and adaptive immune responses
More informationBasic Principles of Tumor Immunotherapy. Ryan J. Sullivan, M.D. Massachusetts General Hospital Cancer Center Boston, MA
Basic Principles of Tumor Immunotherapy Ryan J. Sullivan, M.D. Massachusetts General Hospital Cancer Center Boston, MA Disclosures Consulting Fees: Biodesix, Novartis Pharmaceuticals Other: Boehringer
More informationImmune Checkpoint Inhibitors: The New Breakout Stars in Cancer Treatment
Immune Checkpoint Inhibitors: The New Breakout Stars in Cancer Treatment 1 Introductions Peter Langecker, MD, PhD Executive Medical Director, Global Oncology Clinipace Worldwide Mark Shapiro Vice President
More informationIMMUNOTHERAPY FOR CANCER A NEW HORIZON. Ekaterini Boleti MD, PhD, FRCP Consultant in Medical Oncology Royal Free London NHS Foundation Trust
IMMUNOTHERAPY FOR CANCER A NEW HORIZON Ekaterini Boleti MD, PhD, FRCP Consultant in Medical Oncology Royal Free London NHS Foundation Trust ASCO Names Advance of the Year: Cancer Immunotherapy No recent
More informationEngineered Immune Cells for Cancer Therapy : Current Status and Prospects
When Engineering Meets Immunology Engineered Immune Cells for Cancer Therapy : Current Status and Prospects Yong Taik Lim, Ph.D. Nanomedical Systems Laboratory (http://www.nanomedicalsystems.org) SKKU
More informationFocus on Immunotherapy as a Targeted Therapy. Brad Nelson, PhD BC Cancer, Victoria, Canada FPON, Oct
Focus on Immunotherapy as a Targeted Therapy Brad Nelson, PhD BC Cancer, Victoria, Canada FPON, Oct 18 2018 Disclosures I have nothing to disclose that is relevant to this presentation. Immunology @ Deeley
More informationTumor Immunology. Wirsma Arif Harahap Surgical Oncology Consultant
Tumor Immunology Wirsma Arif Harahap Surgical Oncology Consultant 1) Immune responses that develop to cancer cells 2) Escape of cancer cells 3) Therapies: clinical and experimental Cancer cells can be
More informationRenal Cell Carcinoma: Systemic Therapy Progress and Promise
Renal Cell Carcinoma: Systemic Therapy Progress and Promise Michael B. Atkins, M.D. Deputy Director, Lombardi Comprehensive Cancer Ctr Georgetown University Medical Center Everolimus Rini, Campbell, Escudier.
More informationThe PD-1 pathway of T cell exhaustion
The PD-1 pathway of T cell exhaustion SAMO 18.3.2016 Overview T cell exhaustion Biology of PD-1 Mechanism Ligands expressed on tumor cell and on non-tumor cells other receptor pairs Biomarkers for apd-1/pd-l1
More informationUpdates in Immunotherapy for Urothelial Carcinoma
Updates in Immunotherapy for Urothelial Carcinoma Andrew J Armstrong MD ScM FACP DUA 2018 Copyright 2006 SciMed. Talk Outline Immunotherapy progress in 2017: 5 new approved PD-1/PD-L1 inhibitory agents
More informationScott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION
Scott Abrams, Ph.D. Professor of Oncology, x4375 scott.abrams@roswellpark.org Kuby Immunology SEVENTH EDITION CHAPTER 13 Effector Responses: Cell- and Antibody-Mediated Immunity Copyright 2013 by W. H.
More informationBiomarkers in Imunotherapy: RNA Signatures as predictive biomarker
Biomarkers in Imunotherapy: RNA Signatures as predictive biomarker Joan Carles, MD PhD Director GU, CNS and Sarcoma Program Department of Medical Oncology Vall d'hebron University Hospital Outline Introduction
More informationNovel RCC Targets from Immuno-Oncology and Antibody-Drug Conjugates
Novel RCC Targets from Immuno-Oncology and Antibody-Drug Conjugates Christopher Turner, MD Vice President, Clinical Science 04 November 2016 Uveal Melanoma Celldex Pipeline CANDIDATE INDICATION Preclinical
More informationInnovation in Prevention, Early Detection & Diagnosis of Colorectal Cancer Heidelberg Workshop Session VI, Oncology Pipeline June 6, 2014
Innovation in Prevention, Early Detection & Diagnosis of Colorectal Cancer Heidelberg Workshop Session VI, Oncology Pipeline June 6, 2014 Bernd Mueller MSD Sharp & Dohme, Germany Normal Immune Surveillance:
More informationACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT
ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS Choompone Sakonwasun, MD (Hons), FRCPT Types of Adaptive Immunity Types of T Cell-mediated Immune Reactions CTLs = cytotoxic T lymphocytes
More informationRole of the Pathologist in Guiding Immuno-oncological Therapies. Scott Rodig MD, PhD
Role of the Pathologist in Guiding Immuno-oncological Therapies Scott Rodig MD, PhD Department of Pathology, Brigham & Women s Hospital Center for Immuno-Oncology, Dana-Farber Cancer Institute Associate
More informationIMMUNOTHERAPY IN THE TREATMENT OF CERVIX CANCER. Linda Mileshkin, Medical Oncologist Peter MacCallum Cancer Centre, Melbourne Australia
IMMUNOTHERAPY IN THE TREATMENT OF CERVIX CANCER Linda Mileshkin, Medical Oncologist Peter MacCallum Cancer Centre, Melbourne Australia Distinguishing self from non-self T cells trained in the thymus as
More informationLa revolución de la inmunoterapia: dónde la posicionamos? Javier Puente, MD, PhD
La revolución de la inmunoterapia: dónde la posicionamos? Javier Puente, MD, PhD Hospital Universitario Clinico San Carlos Medical Oncology Department Thoracic & Urological Cancer Unit Complutense University
More informationDisclosures. Immunotherapyin Head & NeckCancer. Actual landscape of systemic treatment in HNSCC. Head andneckcanceris an immunogeneic tumor
Immunotherapyin Head & NeckCancer Disclosures Astra-Zeneca/medimmune: clinical trial BMS: advisory board, clinical trial Merck: advisory board, clinical trial, research funding Carla van Herpen Medical
More informationIMMUNOTHERAPY FOR GASTROINTESTINAL CANCERS
IMMUNOTHERAPY FOR GASTROINTESTINAL CANCERS Dr Elizabeth Smyth Cambridge University Hospitals NHS Foundation Trust ESMO Gastric Cancer Preceptorship Valencia 2018 DISCLOSURES Honoraria for advisory role
More informationRadiation Therapy and Immunotherapy: New Frontiers
Radiation Therapy and Immunotherapy: New Frontiers Nevada Oncology Society Fall Meeting November 16 th, 2017 Anshu K. Jain, MD Radiation Oncologist, Ashland Bellefonte Cancer Center Assistant Clinical
More informationSynergistic combinations of targeted immunotherapy to combat cancer
Synergistic combinations of targeted immunotherapy to combat cancer Myung Ah Lee, M.D., Ph. D Division of Medical Oncology, Hepato-biliary pancreatic cancer center Seoul St. Mary s hospital, The Catholic
More informationNKTR-214 plus NKTR-262, a Scientifically-Guided Rational Combination Approach for Immune Oncology
plus NKTR-262, a Scientifically-Guided Rational Combination Approach for Immune Oncology Jonathan Zalevsky SVP, Biology and Preclinical Development Nektar Therapeutics World Preclinical Congress, 2017
More informationProfessor Mark Bower Chelsea and Westminster Hospital, London
Professor Mark Bower Chelsea and Westminster Hospital, London Cancer immunotherapy & HIV Disclosures: None Lessons for oncology from HIV Awareness and advocacy Activism Rational drug design Prescribing
More informationImmunotherapy versus targeted treatments in metastatic renal cell carcinoma: The return game?
Immunotherapy versus targeted treatments in metastatic renal cell carcinoma: The return game? Sylvie NEGRIER MD, PhD Centre Léon Bérard, Lyon Université Lyon I IMMUNOTHERAPY: A LONG AND WIDING ROAD! WHERE
More informationT cell-mediated immunity
T cell-mediated immunity Overview For microbes within phagosomes in phagocytes.cd4+ T lymphocytes (TH1) Activate phagocyte by cytokines studies on Listeria monocytogenes For microbes infecting and replicating
More informationImmunotherapy in lung cancer. Saurabh maji
Immunotherapy in lung cancer Saurabh maji Worldwide, lung cancer is the most common cause of cancerrelated deaths Small cell lung cancer (SCLC) presents with widespread disease at the time of diagnosis,
More informationUnderstanding Checkpoint Inhibitors: Approved Agents, Drugs in Development and Combination Strategies. Michael A. Curran, Ph.D.
Understanding Checkpoint Inhibitors: Approved Agents, Drugs in Development and Combination Strategies Michael A. Curran, Ph.D. MD Anderson Cancer Center Department of Immunology Disclosures I have research
More informationEmerging Tissue and Serum Markers
Emerging Tissue and Serum Markers for Immune Checkpoint Inhibitors Kyong Hwa Park MD, PhD Medical Oncology Korea University College of Medicine Contents Immune checkpoint inhibitors in clinical practice
More informationManipulating the Tumor Environment
Manipulating the Tumor Environment Vincenzo Bronte Verona University Hospital vincenzo.bronte@univr.it Escape from immune control can be viewed as one of the «Hallmarks of Cancer» D. Hanahan and R. A.
More informationEffector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells
ICI Basic Immunology course Effector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells Abul K. Abbas, MD UCSF Stages in the development of T cell responses: induction
More informationFocused Ultrasound and Cancer Immunotherapy
Focused Ultrasound and Cancer Immunotherapy Overview A number of therapeutic modalities including radiation, radiofrequency and laser-induced heating, cryoablation, and focused ultrasound have been shown
More informationCANCER IMMUNOPATHOLOGY. Eryati Darwin Faculty of Medicine Andalas University
CANCER IMMUNOPATHOLOGY Eryati Darwin Faculty of Medicine Andalas University Padang 18 Mei 2013 INTRODUCTION Tumor: cells that continue to replicate, fail to differentiate into specialized cells, and become
More informationCOURSE: Medical Microbiology, PAMB 650/720 - Fall 2008 Lecture 16
COURSE: Medical Microbiology, PAMB 650/720 - Fall 2008 Lecture 16 Tumor Immunology M. Nagarkatti Teaching Objectives: Introduction to Cancer Immunology Know the antigens expressed by cancer cells Understand
More informationNew insights into CD8+ T cell function and regulation. Pam Ohashi Princess Margaret Cancer Centre
New insights into CD8+ T cell function and regulation Pam Ohashi Princess Margaret Cancer Centre New insights into CD8+ T cell function and regulation Pam Ohashi Princess Margaret Cancer Centre No Disclosures
More informationImmunotherapy for the Treatment of Cancer
Immunotherapy for the Treatment of Cancer Jason Muhitch, PhD Assistant Professor Department of Urology Department of Immunology Roswell Park Comprehensive Cancer Center Oncology for Scientists March 15,
More informationCancer immunity and immunotherapy. General principles
1 Cancer immunity and immunotherapy Abul K. Abbas UCSF General principles 2 The immune system recognizes and reacts against cancers The immune response against tumors is often dominated by regulation or
More informationCytokines: Interferons, Interleukins and Beyond. Michael B. Atkins, MD Georgetown-Lombardi Comprehensive Cancer Center
Cytokines: Interferons, Interleukins and Beyond Michael B. Atkins, MD Georgetown-Lombardi Comprehensive Cancer Center Disclosures Advisory Boards: Bristol-Myers Squibb,Amgen, Novartis, Alkermes, Infinity,
More informationTumors arise from accumulated genetic mutations. Tumor Immunology (Cancer)
Tumor Immunology (Cancer) Tumors arise from accumulated genetic mutations Robert Beatty MCB150 Mutations Usually have >6 mutations in both activation/growth factors and tumor suppressor genes. Types of
More informationThe Really Important Questions Current Immunotherapy Trials are Not Answering
The Really Important Questions Current Immunotherapy Trials are Not Answering David McDermott, MD Beth Israel Deaconess Medical Center Dana Farber/Harvard Cancer Center Harvard Medical School PD-1 Pathway
More informationREPROGRAMING IMMUNITY IN RENAL CELL CARCINOMA
REPROGRAMING IMMUNITY IN RENAL CELL CARCINOMA RETHINKING TYROSINE KINASE INHIBITORS Dr. L.M. Antón Aparicio. Complejo Universitario de La Coruña INTRODUCTION Angiogenesis, which is regulated by a fine
More informationDaratumumab: Uncovering a novel mechanism of action for an approved antibody therapy
Daratumumab: Uncovering a novel mechanism of action for an approved antibody therapy Dr. Kate Sasser, PhD Corporate VP, Translational Research December 14 th, 2017 CD38 is ubiquitously expressed in Myeloma
More informationChapter 10 (pages ): Differentiation and Functions of CD4+ Effector T Cells Prepared by Kristen Dazy, MD, Scripps Clinic Medical Group
FIT Board Review Corner September 2015 Welcome to the FIT Board Review Corner, prepared by Andrew Nickels, MD, and Sarah Spriet, DO, senior and junior representatives of ACAAI's Fellows-In-Training (FITs)
More informationHarnessing the immune system to combat cancer. Gary Middleton, University of Birmingham
Harnessing the immune system to combat cancer Gary Middleton, University of Birmingham Going nowhere fast Vansteenkiste J et al. Lancet Oncol. 2016 Apr 27. pii: S1470-2045(16)00099-1. Immune checkpoints
More informationCheckpoint regulators a new class of cancer immunotherapeutics. Dr Oliver Klein Medical Oncologist ONJCC Austin Health
Checkpoint regulators a new class of cancer immunotherapeutics Dr Oliver Klein Medical Oncologist ONJCC Austin Health Cancer...Immunology matters Anti-tumour immune response The participants Dendritc cells
More informationTumor Immunity and Immunotherapy. Andrew Lichtman M.D., Ph.D. Brigham and Women s Hospital Harvard Medical School
Tumor Immunity and Immunotherapy Andrew Lichtman M.D., Ph.D. Brigham and Women s Hospital Harvard Medical School Lecture Outline Evidence for tumor immunity Types of tumor antigens Generation of anti-tumor
More informationImmunity and Cancer. Doriana Fruci. Lab di Immuno-Oncologia
Immunity and Cancer Doriana Fruci Lab di Immuno-Oncologia Immune System is a network of cells, tissues and organs that work together to defend the body against attacks of foreign invaders (pathogens, cancer
More informationImmunotherapy, an exciting era!!
Immunotherapy, an exciting era!! Yousef Zakharia MD University of Iowa and Holden Comprehensive Cancer Center Alliance Meeting, Chicago November 2016 Presentation Objectives l General approach to immunotherapy
More informationReleasing the Brakes on Tumor Immunity: Immune Checkpoint Blockade Strategies
Releasing the Brakes on Tumor Immunity: Immune Checkpoint Blockade Strategies Jason Muhitch, PhD MIR 509 October 1 st, 2014 Email: jason.muhitch@roswellpark.org 0 Holy Grail of Tumor Immunity Exquisite
More informationPersonalized medicine - cancer immunotherapy
Personalized medicine - cancer immunotherapy Özcan Met, PhD Senior Staff Scientist, Cell Therapy Director Center for Cancer Immune Therapy Department of Hematology Department of Oncology University Hospital
More informationDisclosure Information. Mary L. Disis
Disclosure Information Mary L. Disis I have the following financial relationships to disclose: Consultant for: VentiRx, Celgene, Emergent, EMD Serono Speaker s Bureau for: N/A Grant/Research support from:
More informationMerck Oncology Overview. The Development of MSI-H Cancer Therapy. Development of Anti-Cancer Drugs Forum Tokyo, Japan, 18, February 2017
Merck Oncology Overview The Development of MSI-H Cancer Therapy Development of Anti-Cancer Drugs Forum Tokyo, Japan, 18, February 217 Andrew Joe, MD Executive Director, Late Stage Oncology Merck & Co.,
More informationIMMUNOTHERAPY IN THE TREATMENT OF CERVIX CANCER
Gynecologic Cancer InterGroup Cervix Cancer Research Network IMMUNOTHERAPY IN THE TREATMENT OF CERVIX CANCER Linda Mileshkin, Medical Oncologist Peter MacCallum Cancer Centre, Melbourne Australia Cervix
More informationThe Immune System. Innate. Adaptive. - skin, mucosal barriers - complement - neutrophils, NK cells, mast cells, basophils, eosinophils
Objectives - explain the rationale behind cellular adoptive immunotherapy - describe methods of improving cellular adoptive immunotherapy - identify mechanisms of tumor escape from cellular adoptive immunotherapy
More informationMariano Provencio Servicio de Oncología Médica Hospital Universitario Puerta de Hierro. Immune checkpoint inhibition in DLBCL
Mariano Provencio Servicio de Oncología Médica Hospital Universitario Puerta de Hierro Immune checkpoint inhibition in DLBCL Immunotherapy: The Cure is Inside Us Our immune system prevents or limit infections
More informationDISCLOSURES. Roche/MSD-Merck/Celgene: Research Funding
DISCLOSURES Roche/MSD-Merck/Celgene: Research Funding Roche/Celgene/AstraZeneca/Amgen/MSD/Novartis/Sanofi- Aventis/Pierre Fabré: Advisory Board or Consultant No conflict of interest with respect to this
More informationAdvances in Cancer Immunotherapy for Solid Tumors Expert Perspectives on The New Data Sunday, June 5, 2016
Advances in Cancer Immunotherapy for Solid Tumors Expert Perspectives on The New Data Sunday, June 5, 2016 Supported by an independent educational grant from AstraZeneca Not an official event of the 2016
More informationJune IMMUNE DESIGN The in vivo generation of cytotoxic CD8 T cells (CTLs)
June 2015 IMMUNE DESIGN The in vivo generation of cytotoxic CD8 T cells (CTLs) 1 Forward-looking Statements This presentation contains forward-looking statements with respect to, among other things, our
More informationO DESAFIO DA INOVAÇÃO EM ONCOLOGIA EM PORTUGAL The Challenges of innovative oncology care in Portugal. Gabriela Sousa Oncologia Médica IPO Coimbra
O DESAFIO DA INOVAÇÃO EM ONCOLOGIA EM PORTUGAL The Challenges of innovative oncology care in Portugal Gabriela Sousa Oncologia Médica IPO Coimbra Incidência aumenta 3% ao ano Envelhecimento populacional
More informationPriming the Immune System to Kill Cancer and Reverse Tolerance. Dr. Diwakar Davar Assistant Professor, Melanoma and Phase I Therapeutics
Priming the Immune System to Kill Cancer and Reverse Tolerance Dr. Diwakar Davar Assistant Professor, Melanoma and Phase I Therapeutics Learning Objectives Describe the role of the immune system in cancer
More informationchapter 17: specific/adaptable defenses of the host: the immune response
chapter 17: specific/adaptable defenses of the host: the immune response defense against infection & illness body defenses innate/ non-specific adaptable/ specific epithelium, fever, inflammation, complement,
More informationImmunotherapy of HNC: immune mechanisms and therapeutic targets
Immunotherapy of HNC: immune mechanisms and therapeutic targets Ourania Tsitsilonis, MD, PhD Department of Biology National & Kapodistrian University of Athens What does the Immune System see in Cancer?
More informationCombination Immunotherapy Approaches Chemotherapy, Radiation Therapy, and Dual Checkpoint Therapy
Combination Immunotherapy Approaches Chemotherapy, Radiation Therapy, and Dual Checkpoint Therapy Dr. David B. Page Providence Portland Medical Center Earle A. Chiles Research Institute Funding & Disclosures
More informationONCOS-102 in melanoma Dr. Alexander Shoushtari. 4. ONCOS-102 in mesothelioma 5. Summary & closing
ONCOS-102 in melanoma Dr. Alexander Shoushtari 4. ONCOS-102 in mesothelioma 5. Summary & closing 1 Preliminary data from C824 Activating the Alexander Shoushtari, MD Assistant Attending Physician Melanoma
More informationCurrent practice, needs and future directions in immuno-oncology research testing
Current practice, needs and future directions in immuno-oncology research testing Jose Carlos Machado IPATIMUP - Porto, Portugal ESMO 2017- THERMO FISHER SCIENTIFIC SYMPOSIUM Immune Therapies are Revolutionizing
More informationEmerging Concepts of Cancer Immunotherapy
Emerging Concepts of Cancer Immunotherapy Jeffrey Schlom, Ph.D. Laboratory of Tumor Immunology and Biology (LTIB) Center for Cancer Research National Cancer Institute, NIH Immune Cell Infiltrate in Primary
More informationTumor Immunology: A Primer
Transcript Details This is a transcript of a continuing medical education (CME) activity accessible on the ReachMD network. Additional media formats for the activity and full activity details (including
More informationImmuno-Oncology Clinical Trials Update: Therapeutic Anti-Cancer Vaccines Issue 7 April 2017
Delivering a Competitive Intelligence Advantage Immuno-Oncology Clinical Trials Update: Therapeutic Anti-Cancer Vaccines Issue 7 April 2017 Immuno-Oncology CLINICAL TRIALS UPDATE The goal of this MONTHLY
More informationCombining ADCs with Immuno-Oncology Agents
Combining ADCs with Immuno-Oncology Agents Chad May, PhD Senior Director Targeted Immunotherapy Oncology Research Unit, Pfizer 7 th Annual World ADC October 10, 2016 Cancer-Immunity Cycle Innate Immunity
More informationBASIC MECHANISM OF TUMOR IMMUNE SUPPRESSION
BASIC MECHANISM OF TUMOR IMMUNE SUPPRESSION Zihai Li, M.D., Ph.D. Leader, Cancer Immunology Program Hollings Cancer Center Medical University of South Carolina (MUSC) DISCLOSURE GOALS Understand that immune
More informationImmunotherapy in Colorectal cancer
Immunotherapy in Colorectal cancer Ahmed Zakari, MD Associate Professor University of Central Florida, College of Medicine Medical Director, Gastro Intestinal Cancer Program Florida Hospital Cancer Institute
More informationTHE FUTURE OF IMMUNOTHERAPY IN COLORECTAL CANCER. Prof. Dr. Hans Prenen, MD, PhD Oncology Department University Hospital Antwerp, Belgium
THE FUTURE OF IMMUNOTHERAPY IN COLORECTAL CANCER Prof. Dr. Hans Prenen, MD, PhD Oncology Department University Hospital Antwerp, Belgium DISCLAIMER Please note: The views expressed within this presentation
More informationImmunotherapy in breast cancer. Carmen Criscitiello, MD, PhD European Institute of Oncology Milan, Italy
Immunotherapy in breast cancer Carmen Criscitiello, MD, PhD European Institute of Oncology Milan, Italy Outline Rational for immune-based therapy in breast cancer Immunogenic chemotherapy Targeting immune
More informationEffector T Cells and
1 Effector T Cells and Cytokines Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Cytokines Subsets of CD4+ T cells: definitions, functions, development New
More informationImmunotherapy for the Treatment of Brain Metastases
Society for Immunotherapy of Cancer (SITC) Immunotherapy for the Treatment of Brain Metastases Lawrence G. Lum, MD, DSc Karmanos Cancer Institute and Wayne State University Advances in Cancer Immunotherapy
More informationReviewers' comments: Reviewer #1 (Remarks to the Author):
Reviewers' comments: Reviewer #1 (Remarks to the Author): In the manuscript Rational Combination of CXCL11-Expressing Oncolytic Virus and PD-L1 Blockade Works Synergistically to Enhance Therapeutic Efficacy
More informationTMAC Affimer Drug Conjugates
TMAC Affimer Drug Conjugates A novel and proprietary class of immuno-oncology active, dual mode of action drug conjugates PRS 001 Immune-checkpoint Therapies: Improving Patient Response Rates Despite great
More informationPD-L1 and Immunotherapy of GI cancers: What do you need to know
None. PD-L1 and Immunotherapy of GI cancers: What do you need to know Rondell P. Graham September 3, 2017 2017 MFMER slide-2 Disclosure No conflicts of interest to disclose 2017 MFMER slide-3 Objectives
More informationImmunotherapie: algemene principes
Immunotherapie: algemene principes Prof. dr. Evelien Smits Tumorimmunologie, UAntwerpen 14 Oktober 2017, IKG evelien.smits@uza.be Concept of immune evasion Finn O. J. Ann Oncol. 2012 Sep; 23(Suppl 8):
More informationInnate Immunity and Inflammation
SITC Primer on Tumor Immunology and Biological Therapy of Cancer Innate Immunity and Inflammation Willem Overwijk, Ph.D. MD Anderson Cancer Center Center for Cancer Immunology Research Houston, TX www.allthingsbeautiful.com
More informationImmunotherapy for Genitourinary Cancers
Immunotherapy for Genitourinary Cancers Susan F. Slovin, MD, PhD Genitourinary Oncology Service Sidney Kimmel Center for Prostate and Urologic Cancers Memorial Sloan Kettering Cancer Center New York, New
More informationACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY
ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY The recognition of specific antigen by naïve T cell induces its own activation and effector phases. T helper cells recognize peptide antigens through
More informationInmunoterapia en tumores digestivos no colorrectales
Inmunoterapia en tumores digestivos no colorrectales Santander, 13 de Julio del 2017 Maria Alsina, MD PhD Hospital Universitari Vall d Hebron Outline Introduction Hepatocarcinoma Pancreatic Cancer Gastric
More informationVISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses. Li Wang. Dartmouth Medical School
VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses Li Wang Dartmouth Medical School The B7 Immunoglobulin Super-Family immune regulators APC T cell Co-stimulatory:
More informationMolecular mechanisms of the T cellinflamed tumor microenvironment: Implications for cancer immunotherapy
Molecular mechanisms of the T cellinflamed tumor microenvironment: Implications for cancer immunotherapy Thomas F. Gajewski, M.D., Ph.D. Professor, Departments of Pathology and Medicine Program Leader,
More informationImmunotherapy in Lung Cancer - TLR9 as a therapeutic target -
Immunotherapy in Lung Cancer - TLR9 as a therapeutic target - Wilfried Eberhardt,, MD Head of Outpatient Unit, Dept. of Internal Medicine (Cancer Research) West German Cancer Centre Essen University Hospital
More informationTheodore S. Johnson, MD, PhD
Front-line Therapy of DIPG Using IDO Pathway Inhibitor Indoximod in Combination with Radiation and Chemotherapy American Association of Cancer Research (AACR) 2018 Theodore S. Johnson, MD, PhD Georgia
More information