Enhancing the Clinical Activity of HER2/neu Specific T Cells. William Gwin, MD Internal Medicine, Resident University of Washington
|
|
- Blake Peters
- 5 years ago
- Views:
Transcription
1 Enhancing the Clinical Activity of HER2/neu Specific T Cells William Gwin, MD Internal Medicine, Resident University of Washington
2 Immunotherapy and Cancer Cancer vaccines were originally used in melanoma as an adjuvant treatment to elicit an immune reaction to cancer cells. Adoptive immune therapy was then performed on Melanoma using CD8 clones. Adoptive T cell therapy involves antigenspecific T cells: Selection Ex vivo expansion Adoptive transfer
3 The Tumor Vaccine Group Research focusing on targeting HER2/neu expressing malignancies. Original work focused on protein, peptide, and DNA vaccines targeting the HER-2/neu (HER2) protein. Adoptive T Cell therapy strategies focusing on CD4 cell lines Investigating if T Cell adoptive therapy with a mixed population is as effective as a clonal population in inhibiting growth.
4 HER2/neu ErbB-2 Human Epidermal growth factor Receptor Cell membrane surfacebound receptor tyrosine kinase Normally involved in signal transduction pathways leading to cell growth and differentiation QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.
5 Why Target HER2/neu? Amplification of the HER2/neu gene or its protein product is associated with several cancers percent of breast cancers have an amplification of HER2/neu. Associated with increased disease recurrence and worse prognosis. Overexpression also occurs in: ovarian cancer stomach cancer uterine serous endometrial carcinoma
6 Adoptive T Cell Therapy and HER2/neu Expressing Tumors Previously the most antigenic sequences on HER2/neu have been identified. These antigenic peptides were shown to increase the HER2/neu specific T cell repertoire in vivo. This enabled isolation of increased numbers of antigen specific T cells for ex vivo expansion. It has remained unclear as to which cytokines are best suited during ex vivo culture to promote the generation of high avidity, functional T cells.
7 Hypothesis The ex vivo cytokine environment in which antigenspecific T cells are expanded can greatly influence the function and clinical activity of the T cells in vivo. QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.
8 Cytokines of interest Cytokines Properties Critical T cell growth factor; promotes function of effector CD8+ T cells IL-4 Stimulates differentiation of naïve CD4 T cells into Th2 cells IL-7 Regulates homeostatic proliferation of memory T cells IL-12 Stimulates the production of IFN-g and TNF-a from T cells and NK cells IL-15 Promotes proliferation and effector function of CD8+ T cells, NK, and NKT cells IL-18 Induces IFN-g and accelerated memory CD8+ T cell proliferation 1 Elicits concurrent humoral and cellular responses; promotes differentiation of naïve CD8 T cells into effector T cells
9 Aim: To determine the effects of various culture conditions on the induction of antitumor T cell activity in vivo. Culture conditions evaluated: anti-il-10 +anti-tgfb QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.
10 Isolation, Expansion and Assessment of T Cells 100 μg peptide s.c. Vaccine 1 Day 0 7 Vaccine 2 14 Vaccine 3 21 SAC HARVEST SPLEENS, ISOLATE AND EXPAND T CELLS (IVS on immunizing antigen) DIFFERENT CULTURE CONDITIONS in vivo efficacy
11 Culture Conditions Impact T Cell Therapeutic Efficacy Tumor size (mm 3 ) 1500 Naive +IL-4 +IL IL-12 +IL-15 +IL anti-il-10 +anti-tgf-b p101tc:livemmc (10:1) Time (days)
12 Culture Conditions Impact T Cell Therapeutic Efficacy 1500 Tumor size (mm 3 ) Naive +1 +anti-il-10 45% Inhibition p< %, 67% Inhibition p< %, 39% Inhibition p=0.0019, p= p101tc:livemmc (10:1) Time (days)
13 Conclusions Cytokine addition to the ex vivo culture does improve the therapeutic efficacy in this model. Compared to alone, the most effective culture conditions that induced significantly greater therapeutic efficacy were /anti-il-10 and /IL- 21 cultures.
14 Continued Research What cytokines are being produced by these T cells? What subtypes of T cells are these various culture conditions producing ex vivo? How can we enhance the development of particular T cell subtypes such as Th17 cells?
15 Culture Conditions Impact T Cell Cytokine Secretion 5000 IL Concentration (pg/ml) b All secrete IL-10 except where anti-il-10 mab added B a s e l i n e IL-4 IL-7 IL-12 IL-15 IL-18 T cell culture cytokines 1 IL-10 Anti- Anti- TGF
16 /1 Induce Highly Active Antitumor T Cells Secreting Autoimmune Cytokines IL-17 TNF-a Concentration (pg/ml) Concentration (pg/ml) B a s e l i n e IL-4 IL-7 IL-12 IL-15 IL-18 1 T cell culture c ytokines 0 B a s e l i n e IL-4 IL-7 IL-12 IL-15 IL-18 1 T cell culture cytokines Anti- Anti- IL-10 TGF Anti- Anti- IL-10 TGF Only /1 culture shows high production of IL-17 and TNF-a
17 Conclusions Only /anti-il-10 culture showed low IL-10 production. Blockade of this immunosuppressive cytokine may contribute to enhance the therapeutic efficacy. Only IL2/1 culture showed high IL-17 and TNF-a production. Therapeutic efficacy may be enhanced by the promotion of a pro-inflammatory cytokine environment at the tumor site. Th17 cells are known to produce IL-17 This subpopulation of T cells has been shown to be important in autoimmunity
18 Acknowledgements The Tumor Vaccine Group Dr. Nora Disis Dr. Vy Lai Dr. Ekram Gad
Tumors 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 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 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 informationIDENTIFICATION OF BIOMARKERS FOR EARLY DIAGNOSIS OF BREAST CANCER"
IDENTIFICATION OF BIOMARKERS FOR EARLY DIAGNOSIS OF BREAST CANCER" Edmond Marzbani, MD December 2, 2008 Early diagnosis of cancer Many solid tumors are potentially curable if diagnosed at an early stage
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 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 11 T-Cell Activation, Differentiation, and Memory Copyright 2013 by W. H. Freeman and
More informationTolerance 2. Regulatory T cells; why tolerance fails. FOCiS. Lecture outline. Regulatory T cells. Regulatory T cells: functions and clinical relevance
1 Tolerance 2. Regulatory T cells; why tolerance fails Abul K. Abbas UCSF FOCiS 2 Lecture outline Regulatory T cells: functions and clinical relevance Pathogenesis of autoimmunity: why selftolerance fails
More informationBihong Zhao, M.D, Ph.D Department of Pathology
Bihong Zhao, M.D, Ph.D Department of Pathology 04-28-2009 Is tumor self or non-self? How are tumor antigens generated? What are they? How does immune system respond? Introduction Tumor Antigens/Categories
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 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 informationLecture outline. Immunological tolerance and immune regulation. Central and peripheral tolerance. Inhibitory receptors of T cells. Regulatory T cells
1 Immunological tolerance and immune regulation Abul K. Abbas UCSF 2 Lecture outline Central and peripheral tolerance Inhibitory receptors of T cells Regulatory T cells 1 The immunological equilibrium:
More informationCELLULAR AND MOLECULAR REQUIREMENTS FOR REJECTION OF B16 MELANOMA IN THE SETTING OF REGULATORY T CELL DEPLETION AND HOMEOSTATIC PROLIFERATION
CELLULAR AND MOLECULAR REQUIREMENTS FOR REJECTION OF B16 MELANOMA IN THE SETTING OF REGULATORY T CELL DEPLETION AND HOMEOSTATIC PROLIFERATION Justin Kline 1, Long Zhang 1, and Thomas F. Gajewski 1,2 Departments
More informationNovel RORg Agonists Enhance Anti-Tumor Activity of Adoptive T Cell Therapy
Novel RORg Agonists Enhance Anti-Tumor Activity of Adoptive T Cell Therapy Jacques Moisan, Kinga Majchrzak, Xiao Hu, Rodney Morgan, Xikui Liu, Kellie Demock, Yahong Wang, Charles Lesch, Brian Sanchez,
More informationCellular Immune Parameters Associated with Improved Survival in Breast Cancer Patients after Immunization with a HER2-Specific Vaccine
Cellular Immune Parameters Associated with Improved Survival in Breast Cancer Patients after Immunization with a HER2-Specific Vaccine Tumor Vaccine Group University of Washington John Strickler November
More informationNK mediated Antibody Dependent Cellular Cytotoxicity in HIV infections
NK mediated Antibody Dependent Cellular Cytotoxicity in HIV infections Amy Chung Dr. Ivan Stratov Prof. Stephen Kent ADCC process consists of Target cell QuickTime and a TIFF (Uncompressed) FcγR decompressor
More informationTumor Immunology. Tumor (latin) = swelling
Tumor Immunology Tumor (latin) = swelling benign tumor malignant tumor Tumor immunology : the study of the types of antigens that are expressed by tumors how the immune system recognizes and responds to
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 informationDendritic cells in cancer immunotherapy Aimin Jiang
Dendritic cells in cancer immunotherapy Aimin Jiang Feb. 11, 2014 Dendritic cells at the interface of innate and adaptive immune responses Dendritic cells: initiators of adaptive immune responses Dendritic
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 informationPage 4: Antigens: Self-Antigens The body has a vast number of its own antigens called self-antigens. These normally do not trigger immune responses.
Common Characteristics of B and T Lymphocytes Graphics are used with permission of Pearson Education Inc., publishing as Benjamin Cummings (http://www.aw-bc.com). Page 1: Introduction While B and T lymphocytes
More informationThe Adaptive Immune Responses
The Adaptive Immune Responses The two arms of the immune responses are; 1) the cell mediated, and 2) the humoral responses. In this chapter we will discuss the two responses in detail and we will start
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 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 informationThe g c Family of Cytokines Prof. Warren J. Leonard M.D.
The Family of Cytokines Chief, Laboratory of Molecular Immunology Director, Immunology Center National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services
More informationDeterminants of Immunogenicity and Tolerance. Abul K. Abbas, MD Department of Pathology University of California San Francisco
Determinants of Immunogenicity and Tolerance Abul K. Abbas, MD Department of Pathology University of California San Francisco EIP Symposium Feb 2016 Why do some people respond to therapeutic proteins?
More informationImmunologic principles and immunotherapeutic approaches in ovarian cancer
Hematol Oncol Clin N Am 17 (2003) 1051 1073 Immunologic principles and immunotherapeutic approaches in ovarian cancer Keith L. Knutson, PhD a, *, Tyler J. Curiel, MD, MPH b, Lupe Salazar, MD a, Mary L.
More informationExpansion of HER2/neu-Specific T Cells Ex Vivo Following Immunization with a HER2/neu Peptide-Based Vaccine
translational medicine Expansion of HER2/neu-Specific T Cells Ex Vivo Following Immunization with a HER2/neu Peptide-Based Vaccine Keith L. Knutson and Mary L. Disis Abstract The identification and characterization
More informationT cell maturation. T-cell Maturation. What allows T cell maturation?
T-cell Maturation What allows T cell maturation? Direct contact with thymic epithelial cells Influence of thymic hormones Growth factors (cytokines, CSF) T cell maturation T cell progenitor DN DP SP 2ry
More informationSTATE OF THE ART 4: Combination Immune Therapy-Chemotherapy. Elizabeth M. Jaffee (JHU) James Yang (NCI) Jared Gollob (Duke) John Kirkwood (UPMI)
STATE OF THE ART 4: Combination Immune Therapy-Chemotherapy Elizabeth M. Jaffee (JHU) James Yang (NCI) Jared Gollob (Duke) John Kirkwood (UPMI) Topics for Consideration What are the rules for integrating
More informationImmune surveillance hypothesis (Macfarlane Burnet, 1950s)
TUMOR-IMMUNITÄT A.K. Abbas, A.H. Lichtman, S. Pillai (6th edition, 2007) Cellular and Molecular Immunology Saunders Elsevier Chapter 17, immunity to tumors Immune surveillance hypothesis (Macfarlane Burnet,
More informationImmunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells
Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells Andrew H. Lichtman, M.D. Ph.D. Department of Pathology Brigham and Women s Hospital and Harvard
More informationTITLE: Development of Antigen Presenting Cells for adoptive immunotherapy in prostate cancer
AD Award Number: W8-XWH-5-- TITLE: Development of Antigen Presenting Cells for adoptive immunotherapy in prostate cancer PRINCIPAL INVESTIGATOR: Mathias Oelke, Ph.D. CONTRACTING ORGANIZATION: Johns Hopkins
More informationAntigen Presentation and T Lymphocyte Activation. Abul K. Abbas UCSF. FOCiS
1 Antigen Presentation and T Lymphocyte Activation Abul K. Abbas UCSF FOCiS 2 Lecture outline Dendritic cells and antigen presentation The role of the MHC T cell activation Costimulation, the B7:CD28 family
More informationThird line of Defense. Topic 8 Specific Immunity (adaptive) (18) 3 rd Line = Prophylaxis via Immunization!
Topic 8 Specific Immunity (adaptive) (18) Topics - 3 rd Line of Defense - B cells - T cells - Specific Immunities 1 3 rd Line = Prophylaxis via Immunization! (a) A painting of Edward Jenner depicts a cow
More informationCONTRACTING ORGANIZATION: Johns Hopkins University School of Medicine Baltimore, MD 21205
AD Award Number: DAMD7---7 TITLE: Development of Artificial Antigen Presenting Cells for Prostate Cancer Immunotherapy PRINCIPAL INVESTIGATOR: Jonathan P. Schneck, M.D., Ph.D. Mathias Oelke, Ph.D. CONTRACTING
More informationLESSON 2: THE ADAPTIVE IMMUNITY
Introduction to immunology. LESSON 2: THE ADAPTIVE IMMUNITY Today we will get to know: The adaptive immunity T- and B-cells Antigens and their recognition How T-cells work 1 The adaptive immunity Unlike
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 information- Defined as approaches that enhance, suppress or modify the immune system to treat or cure diseases.
암의면역치료 권병세 Immunotheraphy - Defined as approaches that enhance, suppress or modify the immune system to treat or cure diseases. - Applied for the treatment of cancer, autoimmune diseases, transplant rejection,
More informationCentral tolerance. Mechanisms of Immune Tolerance. Regulation of the T cell response
Immunoregulation: A balance between activation and suppression that achieves an efficient immune response without damaging the host. Mechanisms of Immune Tolerance ACTIVATION (immunity) SUPPRESSION (tolerance)
More informationMechanisms of Immune Tolerance
Immunoregulation: A balance between activation and suppression that achieves an efficient immune response without damaging the host. ACTIVATION (immunity) SUPPRESSION (tolerance) Autoimmunity Immunodeficiency
More informationImmune Regulation and Tolerance
Immune Regulation and Tolerance Immunoregulation: A balance between activation and suppression of effector cells to achieve an efficient immune response without damaging the host. Activation (immunity)
More informationSupplementary Figure 1. Characterization of basophils after reconstitution of SCID mice
Supplementary figure legends Supplementary Figure 1. Characterization of after reconstitution of SCID mice with CD4 + CD62L + T cells. (A-C) SCID mice (n = 6 / group) were reconstituted with 2 x 1 6 CD4
More informationTh17 Pathway Research By Bio-Plex
Th17 Pathway Research By Bio-Plex Zhiyang Shen, Senior Product Manager Bio-Rad Laboratories, Inc 2011 年 6 月 28 日星期二 T helper cell research Timeline: advances on T helper research. Figure depicts some of
More informationMarshall T Bell Research Resident University of Colorado Grand Rounds Nov. 21, 2011
Marshall T Bell Research Resident University of Colorado Grand Rounds Nov. 21, 2011 Most common form of cancer in adults ages 25-29 3-5% of skin cancers but 65-75% of deaths Most common metastasis to small
More informationMucosal Immune System
Exam Format 100 points - 60 pts mandatory; 40 points where 4, 10 point questions will be chosen Some open-ended questions, some short answer. Kuby question Cytokines Terminology How do cytokines achieve
More informationDEVELOPMENT OF CELLULAR IMMUNOLOGY
DEVELOPMENT OF CELLULAR IMMUNOLOGY 1880 s: Antibodies described (dominated studies of immunology until 1960 s) 1958: Journal of Immunology (137 papers) lymphocyte not listed in index Two papers on transfer
More informationImmunotherapy: The Newest Treatment Route
Immunotherapy: The Newest Treatment Route IWMF Patient Forum, Phoenix, AZ Madhav Dhodapkar, MD Professor of Medicine and Immunobiology Chief, Section of Hematology Yale University or the Oldest William
More informationEpidermal Growth Factor Signaling Pathway. R. Armijo, D. Dinh, S. Hindi, S. Jehle, J. Jones & L. Lawson
Epidermal Growth Factor Signaling Pathway R. Armijo, D. Dinh, S. Hindi, S. Jehle, J. Jones & L. Lawson Overview of the EGF Pathway AK LECTURES. EGF Signal Transduction Pathway. Accessed October 10, 2018.
More informationDefective STAT1 activation associated with impaired IFN-g production in NK and T lymphocytes from metastatic melanoma patients treated with IL-2
Defective STAT1 activation associated with impaired IFN-g production in NK and T lymphocytes from metastatic melanoma patients treated with IL-2 SUPPLEMENTARY FIGURES AND TABLES Supplementary Figure S1:
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 informationTITLE: Development of Antigen Presenting Cells for adoptive immunotherapy in prostate cancer
AD Award Number: W8XWH-5-- TITLE: Development of Antigen Presenting Cells for adoptive immunotherapy in prostate cancer PRINCIPAL INVESTIGATOR: Mathias Oelke Ph.D. CONTRACTING ORGANIZATION: Johns Hopkins
More information08/02/59. Tumor Immunotherapy. Development of Tumor Vaccines. Types of Tumor Vaccines. Immunotherapy w/ Cytokine Gene-Transfected Tumor Cells
Tumor Immunotherapy Autologous virus Inactivation Inactivated virus Lymphopheresis Culture? Monocyte s Dendritic cells Immunization Autologous vaccine Development of Tumor Vaccines Types of Tumor Vaccines
More informationThird line of Defense
Chapter 15 Specific Immunity and Immunization Topics -3 rd of Defense - B cells - T cells - Specific Immunities Third line of Defense Specific immunity is a complex interaction of immune cells (leukocytes)
More informationRXi Pharmaceuticals. Immuno-Oncology World Frontiers Conference. January 23, 2018 NASDAQ: RXII. Property of RXi Pharmaceuticals
RXi Pharmaceuticals Immuno-Oncology World Frontiers Conference January 23, 2018 NASDAQ: RXII Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private
More informationChapter 11 CYTOKINES
Chapter 11 CYTOKINES group of low molecular weight regulatory proteins secreted by leukocytes as well as a variety of other cells in the body (8~30kD) regulate the intensity and duration of the immune
More informationDNA vaccine, peripheral T-cell tolerance modulation 185
Subject Index Airway hyperresponsiveness (AHR) animal models 41 43 asthma inhibition 45 overview 41 mast cell modulation of T-cells 62 64 respiratory tolerance 40, 41 Tregs inhibition role 44 respiratory
More informationMOLECULAR MEDICINE REPORTS 2: ,
MOLECULAR MEDICINE REPORTS 2: 615-620, 2009 615 Pre-treatment with cyclophosphamide or OX40 (CD134) costimulation targeting regulatory T cell function enhances the anti-tumor immune effect of adoptively
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 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 informationKinetics of tumor-specific T-cell response development after active immunization in patients with HER-2/neu overexpressing cancers
Clinical Immunology (2007) 125, 275 280 available at www.sciencedirect.com www.elsevier.com/locate/yclim Kinetics of tumor-specific T-cell response development after active immunization in patients with
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 informationIntroduction to Immunology Part 2 September 30, Dan Stetson
Introduction to Immunology Part 2 September 30, 2016 Dan Stetson stetson@uw.edu 441 Lecture #2 Slide 1 of 26 CLASS ANNOUNCEMENT PLEASE NO TREE NUTS IN CLASS!!! (Peanuts, walnuts, almonds, cashews, etc)
More informationErbb2 transgenic mice: a tool to evaluate the potential efficacy of vaccination in the prevention and cure of carcinomas
1 st International MUGEN Conference on Animal Models for Human Immunological Disease Athens, 11 September 2006 Erbb2 transgenic mice: a tool to evaluate the potential efficacy of vaccination in the prevention
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 informationImmunological alterations in mice irradiated with low doses
Immunological alterations in mice irradiated with low doses "Frédéric Joliot-Curie" National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary The structure of the immune system INNATE
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 informationCellular Immune response. Jianzhong Chen, Ph.D Institute of immunology, ZJU
Cellular Immune response Jianzhong Chen, Ph.D Institute of immunology, ZJU Concept of adaptive immune response T cell-mediated adaptive immune response I. Concept of immune response A collective and coordinated
More informationAllergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD.
Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 19: Tolerance, Autoimmunity, and Autoinflammation Prepared
More informationTITLE: MODULATION OF T CELL TOLERANCE IN A MURINE MODEL FOR IMMUNOTHERAPY OF PROSTATIC ADENOCARCINOMA
AD Award Number: DAMD17-01-1-0085 TITLE: MODULATION OF T CELL TOLERANCE IN A MURINE MODEL FOR IMMUNOTHERAPY OF PROSTATIC ADENOCARCINOMA PRINCIPAL INVESTIGATOR: ARTHUR A HURWITZ, Ph.d. CONTRACTING ORGANIZATION:
More informationHow T cells recognize antigen: The T Cell Receptor (TCR) Identifying the TCR: Why was it so hard to do? Monoclonal antibody approach
How T cells recognize antigen: The T Cell Receptor (TCR) Identifying the TCR: Why was it so hard to do By the early 1980s, much about T cell function was known, but the receptor genes had not been identified
More informationA second type of TCR TCR: An αβ heterodimer
How s recognize antigen: The T Cell Receptor (TCR) Identifying the TCR: Why was it so hard to do By the early 1980s, much about function was known, but the receptor genes had not been identified Recall
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 informationT-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes:
Interactions between innate immunity & adaptive immunity What happens to T cells after they leave the thymus? Naïve T cells exit the thymus and enter the bloodstream. If they remain in the bloodstream,
More informationT-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes:
Interactions between innate immunity & adaptive immunity What happens to T cells after they leave the thymus? Naïve T cells exit the thymus and enter the bloodstream. If they remain in the bloodstream,
More informationManipulation of the Immune Response - Immunomodulation -
Manipulation of the Immune Response - Immunomodulation - Janeway s Immunobiology, 9 th ed., 2017. Ivana Novak Nakir Immune system Immune system make components, cells and organs that act together to defend
More informationTumor responses (patients responding/ patients treated)
Table 1. ACT clinical trial tumor responses and toxicities. a Target antigen Cancer(s) Receptor type Tumor responses (patients responding/ patients treated) Immune-mediated toxicities (patients experiencing
More informationTherapeutic efficacy of MUC1- specific CTL and CD137 costimulation. mammary cancer model. Pinku Mukherjee & Sandra Gendler
Therapeutic efficacy of MUC1- specific CTL and CD137 costimulation in a spontaneous mammary cancer model Pinku Mukherjee & Sandra Gendler Goal of Immunotherapy Boosting the low level anti-tumor immune
More informationLicia Rivoltini, MD Unit of Immunotherapy of Human Tumors
Licia Rivoltini, MD Unit of Immunotherapy of Human Tumors The complex network of anti-tumor immunity Innate immunity First line defense Tumor cell Adaptive immunity Specificity & memory Kidd et al., Nature
More informationSheng Chen 1, Feifei Gu 1, Kang Li 1, Kai Zhang 1, Yangyang Liu 1, Jinyan Liang 1, Wei Gao 2, Gang Wu 1* and Li Liu 1*
Chen et al. Journal of Hematology & Oncology (2017) 10:63 DOI 10.1186/s13045-017-0429-8 LETTER TO THE EDITOR A hybrid of B and T lymphoblastic cell line could potentially substitute dendritic cells to
More informationT Cell Activation, Costimulation and Regulation
1 T Cell Activation, Costimulation and Regulation Abul K. Abbas, MD University of California San Francisco 2 Lecture outline T cell antigen recognition and activation Costimulation, the B7:CD28 family
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 informationCell-mediated Immunity
Cellular & Molecular Immunology Cell-mediated Immunity Nicholas M. Ponzio, Ph.D. Department of Pathology & Laboratory Medicine April 6, 2009 Today s Presentation: Overview Cellular Interactions In Humoral
More informationAdoptive cell therapy using genetically modified antigen-presenting cells
Adoptive cell therapy using genetically modified antigen-presenting cells Naoto Hirano Ontario Cancer Institute Princess Margaret Cancer Centre University of Toronto UofT-USP Oncology Conference November
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 informationTITLE: Development of Antigen Presenting Cells for adoptive immunotherapy in prostate cancer
AD Award Number: W8-XWH-5-- TITLE: Development of Antigen Presenting Cells for adoptive immunotherapy in prostate cancer PRINCIPAL INVESTIGATOR: Mathias Oelke,. CONTRACTING ORGANIZATION: Johns Hopkins
More informationParallel session IVB. Chair: Hans Wildiers
Parallel session IVB Biology of ageing and cancer Chair: Hans Wildiers IMMUNOSENESCENCE AND AGEING Tamas Fulop M.D., PhD Research Center on Aging, Division of Geriatrics, University of Sherbrooke, Sherbrooke,
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 informationBiology of Immune Aging
Biology of Immune Aging Jorg J. Goronzy Stanford University Immune deficiency Increase morbidity and mortality from infections Poor vaccine responses Cancer Immune Aging Chronic inflammation Coronary artery
More informationSelf-antigen specific CD8 + T cell precursor frequency determines the quality of the antitumor immune response
ARTICLE Self-antigen specific CD8 + T cell precursor frequency determines the quality of the antitumor immune response Gabrielle A. Rizzuto, 1,3 Taha Merghoub, 1 Daniel Hirschhorn-Cymerman, 1 Cailian Liu,
More informationDevelopment of B and T lymphocytes
Development of B and T lymphocytes What will we discuss today? B-cell development T-cell development B- cell development overview Stem cell In periphery Pro-B cell Pre-B cell Immature B cell Mature B cell
More informationB cell activation and antibody production. Abul K. Abbas UCSF
1 B cell activation and antibody production Abul K. Abbas UCSF 2 Lecture outline B cell activation; the role of helper T cells in antibody production Therapeutic targeting of B cells 3 Principles of humoral
More informationTITLE: Development of a Vaccine Targeting Triple-Negative Breast Cancer
AD Award Number: W81XWH-1-1-7 TITLE: Development of a Vaccine Targeting Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR: Denise Cecil, Ph.D. CONTRACTING ORGANIZATION: University of Washington Seattle,
More informationCONTRACTING ORGANIZATION: Johns Hopkins University School of Medicine Baltimore, MD 21205
AD Award Number: DAMD7---7 TITLE: Development of Artificial Antigen Presenting Cells for Prostate Cancer Immunotherapy PRINCIPAL INVESTIGATOR: Jonathan P. Schneck, M.D., Ph.D. Mathias Oelke, Ph.D. CONTRACTING
More informationAdaptive Immune System
Short Course on Immunology Adaptive Immune System Bhargavi Duvvuri Ph.D IIIrd Year (Immunology) bhargavi@yorku.ca Supervisor Dr.Gillian E Wu Professor, School of Kinesiology and Health Sciences York University,
More informationExamples of questions for Cellular Immunology/Cellular Biology and Immunology
Examples of questions for Cellular Immunology/Cellular Biology and Immunology Each student gets a set of 6 questions, so that each set contains different types of questions and that the set of questions
More informationT Cell Effector Mechanisms I: B cell Help & DTH
T Cell Effector Mechanisms I: B cell Help & DTH Ned Braunstein, MD The Major T Cell Subsets p56 lck + T cells γ δ ε ζ ζ p56 lck CD8+ T cells γ δ ε ζ ζ Cα Cβ Vα Vβ CD3 CD8 Cα Cβ Vα Vβ CD3 MHC II peptide
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 informationIL-12 enhances the generation of tumour antigen-specific Th1 CD4 T cells during ex vivo expansion
Blackwell Science, LtdOxford, UKCEIClinical and Experimental Immunology9-914Blackwell Publishing Ltd, 2424 1352 322329 Original Article K. L. Knutson & M. L. DisisIL-12 activates tumour antigen-specific
More informationProperties & Overview of IRs Dr. Nasser M. Kaplan JUST, Jordan. 10-Jul-16 NM Kaplan 1
Properties & Overview of IRs Dr. Nasser M. Kaplan JUST, Jordan 10-Jul-16 NM Kaplan 1 Major components of IS & their properties Definitions IS = cells & molecules responsible for: 1- Physiologic; protective
More informationDisclosure Statement. I have nothing to disclose
Disclosure Statement I have nothing to disclose Antibody immunity to a panel of oncogenic proteins may predict presence of colon cancer and stage of disease. Goodell V, Lu H, DeLong J, Disis M L. Tumor
More information