Understanding the T cell response to tumors using transnuclear mouse models
|
|
|
- Conrad Hoover
- 5 years ago
- Views:
Transcription
1 Understanding the T cell response to tumors using transnuclear mouse models Stephanie Dougan Dana-Farber Cancer Institute Boston, MA
2 Presenter Disclosure Information Stephanie Dougan The following relationships exist related to this presentation: No Relationships to Disclose 2
3 Melanoma: Responds well to immunotherapy (CTLA-4 and/or PD-1 blockade) Pancreatic ductal adenocarcinoma: Responds poorly to most therapies, notable for being one of few cancer types to fail immunotherapy 7% survival at 5 years
4 Transnuclear mice Advantages of transnuclear mice: 1) T cells are isolated directly from the tumor no time spent in tissue culture 2) TCR genes are in their endogenous loci, under physiological control no other genetic manipulations 3) Multiple, independent lines can be made against the same antigen 4) High-throughput 5) Rapid
5 TRP1 TN mice: models of CD8 T cell response to melanoma TRP1 low TRP1 high Two lines of TN mice derived from CD8 T cells specific for tyrosinase-related protein 1 (TAPDNLGYA) presented by H-2D b Dougan et al., Cancer Immunology Research 2013
6 Two lines of TN mice recognize the same TRP1 epitope, but differ in affinity TRP1 native peptide (conc.) TRP1 high TRP1 low t 1/2 = 41 min t 1/2 = 4.9 min Dougan et al., Cancer Immunology Research 2013
7 Both high and low affinity TRP1 cells can be cytotoxic in 3D tissue culture Cytotoxicity assay using matrigel co-culture of B16 cells with activated CD8 T cells Dougan et al., Cancer Immunology Research 2013
8 Upon activation, both high and low affinity CD8 T cells delay tumor growth in vivo Naive Peptide-activated Anti-CD3/CD28 activated Homeostatic expansion (RAG1-/-) Dougan et al., Cancer Immunology Research 2013
9 TRP1 TN cells transferred into RAG1-/- hosts and reisolated from tumors show markers of exhaustion Increased LAG3, PD-1, Tim3 and CTLA-4 expression Dougan et al., Cancer Immunology Research 2013
10 Candidate gene silencing leads to increased TRP1 accumulation in tumors DGKα LacZ DGKζ TRP1 TN cells (CD45.2) TRP1 high TRP1 low CD8 Collaboration with Kai Wucherpfennig
11 Silencing of Ppp2r2d enhances anti-tumor effect of TRP1 TN cells p=0.007 LacZ control Ppp2r2d Wet Weight (g) LacZ Ppp2r2d Collaboration with Kai Wucherpfennig
12 How does TCR affinity affect activation and anti-tumor activity? T cell TCR Altered Peptide Ligands Native peptide: TAPDNLGYA Reference (M9): TAPDNLGYM K8: TAPDNLGKM Anchor Residues APC Peptide MHC I Mean fluorescence H-2Db Peptide Dilution Factor M9 Nat K8 Negative
13 TRP1 high T cells activated by M9 or K8 delay growth of B Tumor Volume (mm3) Adoptive Transfer Days since tumor inoculation No treatment K8 high M9 high
14 K8 activation results in more long-term survivors Total number mice Long term survivors Survived rechallenge TRP1low K8 TRP1high K8 TRP1low M9 TRP1high M / / / TRP1 tetramer Memory T cells in spleen 3 months after transfer CD8
15 K8 activated TRP1high and TRP1low cells remain PD-1 low TRP1high A1 native A3 K8 PD-1 TRP1low Cell trace violet A1 native A3 K8 PD-1 Cell trace violet
16 Summary for melanoma Both high and low affinity CD8 T cells are capable of mounting antitumor responses. TRP1 transnuclear mice are good models to study anti-tumor immunity. K8 activation leads to good control of tumor growth and induction of long-term memory. K8 activated CD8 cells are PD-1 low and have a unique transcriptional profile. Can we exploit the genes differentially regulated in K8 activated cells to enhance CD8 T cell memory?
17 Pancreatic ductal adenocarcinoma Poor prognosis Highly metastatic Hypovascular Dense stroma Poor drug delivery Very few T cell infiltrates (mostly Tregs)
18 Transnuclear mice from pancreatic tumor-infiltrating CD4 T cells Panc CD4a: TCR Vβ14+ Germline-transmitting chimera Normal frequency of Foxp3+ Tregs
19 PancCD4A cells specifically infiltrate pancreatic tumors accumulation % PancCD4A / total CD4+ Panc02 B16 draining LN Panc02 B16 TILs B16 melanoma Panc02 pancreatic tumor
20 Orthotopic injections of cancer cells directly into pancreas 609 SNPs ~30 SNPs
21 CD8 T cells are important in control of orthotopic Panc Tumor weight (g) Rag2-/- B6 Tumor weight (g) isotype CD4 depletion CD8 depletion 0 0
22 PancCD4a cells affect tumor growth only when given early PancCD4a cells given 5 days after tumor PancCD4a cells given 1 day after tumor entire pancreas pancreatic tumor untreated naive T cells Activated T cells 0 untreated naïve T cells 0 untreated activated T cells
23 Transferred PancCD4a cells proliferate in pancreas draining LN spleen pancreas dln tumor naïve PancCD4a Celltrace violet activated PancCD4a no T cells CD45.1
24 VHH Antibodies Readily expressed in bacteria Small size (15 kda) allows deep tissue penetration Rapidly cleared after injection No FcR or complement engagement or cross-linking Expressed with LPETG tag for modification by sortase In collaboration with Hidde Ploegh, Jessica Ingram and Michael Dougan
25 Alpaca antibody B3 is specific for PD-L1 Hidde Ploegh, Jessica Ingram and Michael Dougan
26 Pancreatic tumor cells express PD-L1 Panc02 KPC Cell lines Resected orthotopic tumors B3 (alpaca anti-pdl1)
27 Alpaca-derived anti-pd-l1 conjugated to IL-2 sortase Fluorescent Tags Biotin Protein linking Pancreatic cancer neoantigens adjuvant 18 F cytokines In collaboration with Hidde Ploegh, Jessica Ingram and Michael Dougan
28 Very low dose B3-IL2 decreases pancreatic tumor burden isotype Weight (g) ** * B3 B3IL-2 B3IL-2 +PancCD4A
29 Very low dose B3-IL2 allows infiltration of PancCD4a T cells CD25 CD4 gated on CD45.1 transferred cells
30 Immunotherapy for pancreatic cancer Anti-PDL1 alpaca antibodies can target immunotherapeutic agents to pancreatic tumors. Targeted IL-2 increases CD8 T cells, increases T cell trafficking to tumors, and decreases overall tumor size. Transnuclear PancCD4a cells can be used to monitor CD4 T cell trafficking and lineage choice. Intratumoral anti-cd40 generates systemic immune responses against nontreated tumors and may synergize with targeted radiation therapy.
31 Acknowledgements Paul Tyler Mariah Servos Patrick Bruck Eleanor Clancy-Thompson Cherry Ng Albert Li Hidde Ploegh (Whitehead) Rudolf Jaenisch (Whitehead) Kai Wucherpfennig (DFCI) Wilfred Ngwa (DFCI/BWH) Rajiv Kumar (DFCI) Michael Dougan (MGH) Jessica Ingram (Whitehead) Anirban Maitra (MDACC) Funding Claudia Adams Barr Award for Cancer Research Pancreatic Cancer Action Network Pathway to Leadership Award Melanoma Research Alliance Young Investigator Award HMS Shore Fellowship
VISTA, 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:
Regulation 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,
Cancer 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
T 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
Molecular 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,
TITLE: 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:
Tumor 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
Therapeutic 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
Tim-3 as a target for tumor immunotherapy
Tim-3 as a target for tumor immunotherapy Ana Carrizosa Anderson Brigham and Women s Hospital Harvard Medical School Disclosures A portion of the work has been performed as part of a sponsored research
Restoring Immune Function of Tumor-Specific CD4 + T Cells during Recurrence of Melanoma
Restoring Immune Function of Tumor-Specific CD4 + T Cells during Recurrence of Melanoma Goding SR et al. J Immunol 2013; 190:4899-4909 C. Nikolowsky Christian Doppler Laboratory for Cardiac and Thoracic
Scott 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
MHC Tetramers and Monomers for Immuno-Oncology and Autoimmunity Drug Discovery
MHC Tetramers and Monomers for Immuno-Oncology and Autoimmunity Drug Discovery Your Partner in Drug Discovery and Research MHC Tetramer Background T-Cell Receptors recognize and bind to complexes composed
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
Creating New Tools to Fight an Old Foe: Cancer Immunotherapy with Alpaca Antibodies
75 years!! www.asa3.org Creating New Tools to Fight an Old Foe: Cancer Immunotherapy with Alpaca Antibodies Presented by: Dr. Craig M. Story, Gordon College Cancer Cell T cell Talk Outline What is cancer?
Machine Learning For Personalized Cancer Vaccines. Alex Rubinsteyn February 9th, 2018 Data Science Salon Miami
Machine Learning For Personalized Cancer Vaccines Alex Rubinsteyn February 9th, 2018 Data Science Salon Miami OpenVax @ Mount Sinai Focus: personalized cancer vaccines Machine learning for immunology Cancer
International Society of Breast Pathology. Immune Targeting in Breast Cancer. USCAP 2017 Annual Meeting
International Society of Breast Pathology USCAP 2017 Annual Meeting Immune Targeting in Breast Cancer Ashley Cimino-Mathews, MD Assistant Professor of Pathology and Oncology The Johns Hopkins Hospital
FOCiS. Lecture outline. The immunological equilibrium: balancing lymphocyte activation and control. Immunological tolerance and immune regulation -- 1
1 Immunological tolerance and immune regulation -- 1 Abul K. Abbas UCSF FOCiS 2 Lecture outline Principles of immune regulation Self-tolerance; mechanisms of central and peripheral tolerance Inhibitory
Nobel Prize in Physiology or Medicine 2018
Nobel Prize in Physiology or Medicine 2018 Arunika Mukhopadhaya The Nobel Prize in Physiology or Medicine for the year 2018 was awarded to James P Allison of the United States and Tasuku Honjo of Japan
T Lymphocyte Activation and Costimulation. FOCiS. Lecture outline
1 T Lymphocyte Activation and Costimulation Abul K. Abbas, MD UCSF FOCiS 2 Lecture outline T cell activation Costimulation, the B7:CD28 family Inhibitory receptors of T cells Targeting costimulators for
Determinants 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?
Emerging 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
The Enhancement of Anti-Tumor Activities of Selinexor when Combined with Immune Checkpoint Inhibitors
The Enhancement of Anti-Tumor Activities of Selinexor when Combined with Immune Checkpoint Inhibitors Trinayan Kashyap, Karyopharm Therapeutics Yu-Tzu Tai and Kenneth Anderson, Dana Farber Boston Matthew
Posters and Presentations
Posters and Presentations June 2017: American Society of Clinical Oncology (ASCO) Annual - Preliminary Correlative Analysis of PD-L1 expression from the SUNRISE Study. View April 2017: American Association
Novel 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
Disclosure 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:
Adoptive 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
Supplemental Materials
Supplemental Materials Programmed death one homolog maintains the pool size of regulatory T cells by promoting their differentiation and stability Qi Wang 1, Jianwei He 1, Dallas B. Flies 2, Liqun Luo
Discover the PD-1 pathway and its role in cancer 105/15 -ONCO- 07/15
Discover the PD-1 pathway and its role in cancer 105/15 -ONCO- 07/15 Immunology in cancer The role of immunology in cancer Evolving knowledge of the immune system has provided a better understanding of
Radiation 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
IMMUNOTHERAPY 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
NKTR-255: Accessing The Immunotherapeutic Potential Of IL-15 for NK Cell Therapies
NKTR-255: Accessing The Immunotherapeutic Potential Of IL-15 for NK Cell Therapies Saul Kivimäe Senior Scientist, Research Biology Nektar Therapeutics NK Cell-Based Cancer Immunotherapy, September 26-27,
Dendritic cell subsets and CD4 T cell immunity in Melanoma. Ben Wylie 1 st year PhD Candidate
Dendritic cell subsets and CD4 T cell immunity in Melanoma Ben Wylie 1 st year PhD Candidate Melanoma Melanoma is the 4 th most common cancer in Australia. Current treatment options are ineffective resulting
2/16/2018. 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
Pancreatic Adenocarcinoma: What`s hot
Pancreatic Adenocarcinoma: What`s hot Eva Karamitopoulou-Diamantis Institute of Pathology University of Bern 11.09.2018, 30th ECP, Bilbao Pancreatic Cancer and the Microbiome The Pancreatic Cancer Microbiome
Immune 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
T cell development October 28, Dan Stetson
T cell development October 28, 2016 Dan Stetson stetson@uw.edu 441 Lecture #13 Slide 1 of 29 Three lectures on T cells (Chapters 8, 9) Part 1 (Today): T cell development in the thymus Chapter 8, pages
SUPPLEMENTARY INFORMATION
Table S1: Combination Immunotherapy: Small Molecules that Boost Immune Response in Combination with Other Agents Target Compound (MOA) NLG919 and indoximod 1- MT Combination Model Observation Reference
Radiation 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
Synergistic 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
Blocking antibodies and peptides. Rat anti-mouse PD-1 (29F.1A12, rat IgG2a, k), PD-
Supplementary Methods Blocking antibodies and peptides. Rat anti-mouse PD-1 (29F.1A12, rat IgG2a, k), PD- L1 (10F.9G2, rat IgG2b, k), and PD-L2 (3.2, mouse IgG1) have been described (24). Anti-CTLA-4 (clone
Nature Medicine doi: /nm.3957
Supplementary Fig. 1. p38 alternative activation, IL-21 expression, and T helper cell transcription factors in PDAC tissue. (a) Tissue microarrays of pancreatic tissue from 192 patients with pancreatic
General 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
The 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
5% 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
Effector 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
Shiv Pillai Ragon Institute, Massachusetts General Hospital Harvard Medical School
CTLs, Natural Killers and NKTs 1 Shiv Pillai Ragon Institute, Massachusetts General Hospital Harvard Medical School CTL inducing tumor apoptosis 3 Lecture outline CD8 + Cytotoxic T lymphocytes (CTL) Activation/differentiation
Autoimmunity. Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens
Autoimmunity Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens Autoimmune disease can be caused to primary defects in B cells, T cells and possibly
Adaptive immune responses: T cell-mediated immunity
MICR2209 Adaptive immune responses: T cell-mediated immunity Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will discuss the T-cell mediated immune response, how it is activated,
T-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,
T-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,
IMMUNOTHERAPY 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
PD-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
FcγRIIIA (CD16)-expressing monocytes mediate the depletion of tumor-infiltrating Tregs via ipilimumab-dependent ADCC in melanoma patients
FcγRIIIA (CD16)-expressing monocytes mediate the depletion of tumor-infiltrating Tregs via ipilimumab-dependent ADCC in melanoma patients Emanuela Romano Department of Oncology University of Lausanne and
Supplementary Figures
Supplementary Figures Supplementary Figure 1. NKT ligand-loaded tumour antigen-presenting B cell- and monocyte-based vaccine induces NKT, NK and CD8 T cell responses. (A) The cytokine profiles of liver
Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured
Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured under Th0, Th1, Th2, Th17, and Treg conditions. mrna
Focus 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
PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland
Award Number: W81XWH-12-1-48 TITLE: Evaluation of the immunologic impact of RAF Inhibitors to Guide Optimal Combination of RAF inhibitors and Immunotherapy for the treatment of Advanced Melanoma PRINCIPAL
The 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
Understanding 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
COURSE: 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
Licia 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
TITLE: 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
Cancer immunotherapy with oncolytic viruses: more than just lysis
Cancer immunotherapy with oncolytic viruses: more than just lysis Dmitriy Zamarin MD PhD Assistant Attending, Immune Therapeutics Center Memorial Sloan-Kettering Cancer Center New York, NY BCAN Think Tank
Cancer Immunotherapy: Active Immunization Approaches
Cancer Immunotherapy: Active Immunization Approaches Willem W. Overwijk, PhD Department of Melanoma Medical Oncology MD Anderson Cancer Center Houston, TX, USA Disclosures No relevant financial relationships
Exploring Therapeutic Combinations with anti-ctla-4 Antibody
Exploring Therapeutic Combinations with anti-ctla-4 Antibody Padmanee Sharma, MD, PhD Associate Professor GU Medical Oncology and Immunology M. D. Anderson Cancer Center isbtc Hot Topic Symposium October
NKTR-255: Accessing IL-15 Therapeutic Potential through Robust and Sustained Engagement of Innate and Adaptive Immunity
NKTR-255: Accessing IL-15 Therapeutic Potential through Robust and Sustained Engagement of Innate and Adaptive Immunity Peiwen Kuo Scientist, Research Biology Nektar Therapeutics August 31 st, 2018 Emerging
TCR, MHC and coreceptors
Cooperation In Immune Responses Antigen processing how peptides get into MHC Antigen processing involves the intracellular proteolytic generation of MHC binding proteins Protein antigens may be processed
IMMUNOTHERAPY 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
Excerpt from MACS&more Vol 17 1/2016. Kenji Miki¹, Koji Nagaoka¹, Hermann Bohnenkamp², Takayuki Yoshimoto³, Ryuji Maekawa¹*, and Takashi Kamigaki⁴
Excerpt from MCS&more Vol 17 1/2016 Dendritic cells pulsed with induce both OV-specific CD4 + and CD8 + T cells and cause antitumor effects in a mouse model of lymphoma Kenji Miki¹, Koji Nagaoka¹, Hermann
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 New insights into CD8+ T cell function and regulation Pam Ohashi Princess Margaret Cancer Centre No Disclosures
CELLULAR 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
T cell Receptor. Chapter 9. Comparison of TCR αβ T cells
Chapter 9 The αβ TCR is similar in size and structure to an antibody Fab fragment T cell Receptor Kuby Figure 9-3 The αβ T cell receptor - Two chains - α and β - Two domains per chain - constant (C) domain
Emerging 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
Adaptive (acquired) immunity. Professor Peter Delves University College London
Adaptive (acquired) immunity Professor Peter Delves University College London p.delves@ucl.ac.uk Haematopoiesis Haematopoiesis Lymphocytes = adaptive response Recognition of pathogens by adaptive cells,
Tumor 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
Active STAT5 promotes long lived cytotoxic CD8 T cells that induce regression of autochthonous mouse melanoma.
Active STAT5 promotes long lived cytotoxic CD8 T cells that induce regression of autochthonous mouse melanoma. SITC 211 Grégory Verdeil No relationships to disclose T cell adoptive transfer for cancer
Lecture 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:
The 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
Immunology and Immunotherapy 101 for the Non-Immunologist
Immunology and Immunotherapy 101 for the Non-Immunologist Stephen P. Schoenberger, Ph.D La Jolla Institute for Allergy and Immunology & UCSD Moores Cancer Center Disclosures Human Longevity Inc: Salary
Immunotherapeutic barriers at the level of the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D.
Immunotherapeutic barriers at the level of the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D. Professor, Departments of Pathology and Medicine Program Leader, Immunology and Cancer Program of the
WIN 2015 Symposium Radiation and immunology: a new therapeutic partnership
WIN 215 Symposium Radiation and immunology: a new therapeutic partnership Dr. Ralph Weichselbaum Conflict of Interest Nothing to Disclose Limitations of Radiotherapy Radiotherapy cannot be given in high
Therapeutic PD L1 and LAG 3 blockade rapidly clears established blood stage Plasmodium infection
Supplementary Information Therapeutic PD L1 and LAG 3 blockade rapidly clears established blood stage Plasmodium infection Noah S. Butler, Jacqueline Moebius, Lecia L. Pewe, Boubacar Traore, Ogobara K.
Immuno-Oncology Therapies and Precision Medicine: Personal Tumor-Specific Neoantigen Prediction by Machine Learning
Immuno-Oncology Therapies and Precision Medicine: Personal Tumor-Specific Neoantigen Prediction by Machine Learning Yi-Hsiang Hsu, MD, SCD Sep 16, 2017 yihsianghsu@hsl.harvard.edu HSL GeneticEpi Center,
Enhanced Cancer Vaccine Effectiveness with NKTR-214, a CD122-Biased Cytokine
Enhanced Cancer Vaccine Effectiveness with NKTR-214, a CD122-Biased Cytokine Jonathan Zalevsky SVP, Biology and Preclinical Development Nektar Therapeutics SMI Cancer Vaccines, September 2017 Nektar Therapeutics
Immunity 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
Interleukin-2 Single Agent and Combinations
Interleukin-2 Single Agent and Combinations Michael K Wong MD PhD Norris Cancer Center University of Southern California mike.wong@med.usc.edu Disclosures Advisory Board Attendance Merck Bristol Myers
Immunotherapy 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
Immunotherapy 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
DEVELOPMENT 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
Basic 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
Antigen specific anti-spas-1 CD8 T cell responses to in situ vaccination using irreversible electroporation (IRE) of prostate tumors
Antigen specific anti-spas-1 CD8 T cell responses to in situ vaccination using irreversible electroporation (IRE) of prostate tumors Joseph R. Slaughter slaug044@umn.edu M.D. Candidate, Class of 2020 University
Immunology 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
Immunology Lecture 4. Clinical Relevance of the Immune System
Immunology Lecture 4 The Well Patient: How innate and adaptive immune responses maintain health - 13, pg 169-181, 191-195. Immune Deficiency - 15 Autoimmunity - 16 Transplantation - 17, pg 260-270 Tumor
Depletion of FAP + cells reduces immunosuppressive cells and improves metabolism and functions CD8 + T cells within tumors
/, Vol. 7, No. 17 Depletion of FAP + cells reduces immunosuppressive cells and improves metabolism and functions CD8 + T cells within tumors Ying Zhang 1,2, Hildegund C.J. Ertl 2 1 Gene Therapy and Vaccines
Accepted Manuscript. Next Steps for Immune Checkpoints in Hepatocellular Carcinoma. Patricia M. Santos, Lisa H. Butterfield
Accepted Manuscript Next Steps for Immune Checkpoints in Hepatocellular Carcinoma Patricia M. Santos, Lisa H. Butterfield PII: S0016-5085(18)35218-1 DOI: https://doi.org/10.1053/j.gastro.2018.11.008 Reference:
T 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
Focused 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
Supplemental Table I.
Supplemental Table I Male / Mean ± SEM n Mean ± SEM n Body weight, g 29.2±0.4 17 29.7±0.5 17 Total cholesterol, mg/dl 534.0±30.8 17 561.6±26.1 17 HDL-cholesterol, mg/dl 9.6±0.8 17 10.1±0.7 17 Triglycerides,
Highlights from AACR 2015: The Emerging Potential of Immunotherapeutic Approaches in Non-Small Cell Lung Cancer
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
Enhancing the Clinical Activity of HER2/neu Specific T Cells. William Gwin, MD Internal Medicine, Resident University of Washington
Enhancing the Clinical Activity of HER2/neu Specific T Cells William Gwin, MD Internal Medicine, Resident University of Washington Immunotherapy and Cancer Cancer vaccines were originally used in melanoma