Clinical Translation of a Mammaglobin A DNA Vaccine for Breast Cancer Therapy
|
|
|
- Violet Pope
- 5 years ago
- Views:
Transcription
1 Clinical Translation of a Mammaglobin A DNA Vaccine for Breast Cancer Therapy William E. Gillanders, M.D. Recombinant DNA Advisory Committee December 14, 25
2 Overview This is a phase I dose ranging vaccine safety trial of a mammaglobin A DNA vaccine The broad objective of the study is to identify a safe and immunologically active dose of the mammaglobin A DNA vaccine that can be used in future studies
3 Mammaglobin A A Tissue Expression Ovary Uterus Placenta Lung B5 589 Breast Breast cancer Watson MA et al, Cancer Research 1996; 56:86
4 Mammaglobin A A Tissue Expression Breast Breast Cancer Ovary Placenta Uterus Testis Prostate PBL Lymph node Spleen Thymus Lung Colon Bladder Kidney Liver Brain No template GAPDH hmam Watson MA et al, Cancer Research 1996; 56:86
5 Mammaglobin A A Tissue Expression
6 Mammaglobin A A Tissue Expression Watson MA et al, Cancer Research 1999; 59:328
7 Mammaglobin A A Tissue Expression Ductal carcinoma in situ Well differentiated ductal carcinoma Poorly differentiated ductal carcinoma Watson MA et al, Cancer Research 1999; 59:328
8 Summary Mammaglobin A is expressed almost exclusively in normal breast epithelium and breast cancer Mammaglobin A is overexpressed in up to 8% of primary and metastatic breast cancers Mammaglobin A overexpression appears to be consistent in all stages of breast cancer
9 Presentation of Mammaglobin A HBL 1 AU 565 M DA M B 361 M DA M B 415 M CF 7 M DA M B Specific Lysis (%) Specific Lysis (%) Jaramillo A et al, International Journal of Cancer 22; 12:499
10 Mammaglobin A reactive T cells Frequency (reciprocal) Patients Controls CD8+ T cells CD4+ T cells Jaramillo A et al, International Journal of Cancer 22; 12:499
11 MHC Class I trimeric structure Peptide Heavy chain β 2 m
12 Predicting mammaglobin A A epitopes
13 Mammaglobin HLA A3 A3 peptides HLA A3 Binding Peptides Derived from Mammaglobin A Peptide Amino Acid Position Peptide Sequence HLA A3 binding score Mam A PLLENVISK 27. Mam A KTINPQVSK 6.75 Mam A KLLMVLMLA 4.5 Mam A TTNAIDELK 1.5 Mam A LMVLMLAAL 1.35 Mam A FLNQTDETL.6 Mam A LMLAALSQH.45 Mam A AIDELKECF.3 Jaramillo A et al, International Journal of Cancer 22; 12:499
14 Membrane Stabilization Assay Mam A3.1 Mam A3.2 Mam A3.3 Mam A3.4 Mam A3.5 Mam A3.6 Mam A3.7 Mam A3.8 Influenza Mean Fluorescence Shift Jaramillo A et al, International Journal of Cancer 22; 12:499
15 Mammaglobin A reactive T cells Frequency of CD8 T cells reactive to mammaglobin A derived peptides in the peripheral blood of HLA A3 breast cancer patients Patients Controls A A3.2 A HLA A3 peptides A A3.5 A A3.7 7 A Influenza
16 Summary CD8 and CD4 T cells specific for mammaglobin A can be generated in vitro from the peripheral blood of breast cancer patients confirming that the immune system can recognize this antigen Analyses of peripheral blood from breast cancer patients confirm that breast cancer patients have higher frequencies of mammaglobin A reactive T cells
17 Advantages of DNA Vaccination Safety Generic manufacture with high purity and stability relative to protein vaccines Cost advantage Vaccination with full length cdna avoids the requirement of MHC restriction
18 Humanized Mouse Model C57BL/6 mice transgenic for Human HLA A2 X C57BL/6 mice transgenic for Human CD8 Human HLA A2 + /CD8+ C57BL/6 mice Expression of HLA A2 on all tissues Tissue specific expression of human CD8 on CD8 + T cells Facilitates recognition of human MHC by mouse CD8 + T cells
19 Humanized Mouse Model Day : DNA vaccine Day 7: DNA vaccine Day 14: DNA vaccine Day 21: DNA vaccine Day 28: Immune Analysis
20 Humanized Mouse Model Control Vaccinated A 2 1 Narayanan et al, Journal of the National Cancer Institute 24; 96:1388
21 Breast Cancer Xenograft Model Day : Tumor Challenge HBL 1 or MDA 231 cells resuspended in basement membrane Day 14: Adoptive transfer of 4 x 1 7 spleen cells from vaccinated mice Tumor size measured by calipers weekly
22 Breast Cancer Xenograft Model Narayanan et al, Journal of the National Cancer Institute 24; 96:1388
23 Phase I Clinical Trial This is a phase I dose ranging vaccine safety trial of a mammaglobin A DNA vaccine The broad objective of the study is to identify a safe and immunologically active dose of the mammaglobin A DNA vaccine that can be used in future studies
24 Objectives Evaluate the safety of the mammaglobin A DNA vaccine Assess the in vivo immune response induced by the mammaglobin A DNA vaccine by evaluation of the CD8, CD4 and Treg immune responses
25 Objectives Assess the impact of mammaglobin A DNA vaccination on breast cancer tumor markers, including circulating breast cancer cells Evaluate enrolled patients for time to disease progression following vaccination with the mammaglobin A DNA vaccine
26 Patient Selection Patients with stage IV breast cancer are eligible for enrollment Eligible patients will have metastatic breast cancer that has been stable for at least 28 days after chemotherapy, or on hormonal therapy
27 Dose Escalation This trial is a dose ranging study of four doses of the mammaglobin A DNA vaccine Four groups of at least three patients will be vaccinated with mammaglobin A DNA delivered intramuscularly at four different dose levels (15 μg, 5 μg, 15 μg, 5 mg) every three weeks for four injections
28 Dose Escalation Dose escalation will only occur when the final patient at the prior dose level has safely completed all four injections and no dose limiting toxicity (DLT) has been noted in more than one patient at the final postvaccination visit
29 Immune Monitoring ELISPOT assays, intracellular cytokine expression analyses using multiparameter flow cytometry, and peptide MHC tetramer analyses will be used to assess the antigen specific T cell response to the mammaglobin A DNA vaccine
30 Anticipated Toxicity Based on experience with DNA vaccines in phase I clinical trials we expect toxicity to be limited to grade 1 vaccine site reactions Other reactions that have been described include hyperglycemia, hypoalbuminemia, myalgia, chills, allergic rhinitis, cough, headache and pruritis
31 Safety Safety defined as the absence of sever toxicity (grade 3 or greater) using the National Institutes of Health Common Toxicity Criteria
32 Optimal Dose The dose of mammaglobin A DNA vaccine that is associated with the maximum immune response will be considered optimal If there is no clear difference in the immune response to two or more doses of mammaglobin A DNA vaccine, the lowest dose of mammaglobin A DNA vaccine that is associated with the maximum immune response will be considered optimal
33 ping mammaglobin mammaglobin A A vector DraIII (4827) Bsp HI (4 771) NruI (4636) Bsp DI (46 ) Kanamycin Ori Sma I (4 419 ) X mai (4 417) Bsm I (4411) EcoNI (438) Cfr1I (4335) Bsr FI (4335) Bsm I (4334) K a na m yc in Pvu I (4295) HindIII (4171) Stu I (3669) AatI (3669 ) BanI (3465) BclI (3387) PmeI (3378) ping Mammaglobin 4851 bp Apa I (3373) Bsp 12I (3369 ) XbaI (336 3) BsrBI (3356 ) Not I (3351) Bst XI (334 6) EcoRV (3336) EcoRI (3324 ) Bsu 36 I (92) Bsp HI (178) O ri Alw 44I (584) Apa LI (584 ) Asp 7 (3143) Sno I (584 ) EcoRI (3324) Promoter M am m a globin Asp 7 (383) NheI (2919 ) Bsa I (29) Mlu I (2881) Bss HII (286) ping Mammaglobin 4851 bp DrdI (796) BglII (193) Bsp DI (1173) Bsr GI (1285) Ssp BI (1285) Sp e I (134 1) Mammaglobin Bss HII (284 ) Sca I (279) HpaI (276) P romo te r NdeI (1576) Sn abi (1682) PvuII (276) Bsa AI (1682) BfrI (2675) Ba ni (187) AflII (2675) BpmI (1955) NheI (2919) Exon BpmI (2488) Sa p I (2459 ) MroI (2441) Bsp EI (2441) E x on KspI (1997) Sa c II (19 97) Sph I (297) Bse AI (2441) Bp u112i (216 2) Acc III (244 1) CelII (2162) Bsa AI (24 36) Esp I (2162) XcmI (225) PpuMI (2333)
34
Cover Page. The handle holds various files of this Leiden University dissertation
Cover Page The handle http://hdl.handle.net/1887/35908 holds various files of this Leiden University dissertation Author: Soema, Peter Title: Formulation of influenza T cell peptides : in search of a universal
Immunology - Lecture 2 Adaptive Immune System 1
Immunology - Lecture 2 Adaptive Immune System 1 Book chapters: Molecules of the Adaptive Immunity 6 Adaptive Cells and Organs 7 Generation of Immune Diversity Lymphocyte Antigen Receptors - 8 CD markers
Foundations in Microbiology
Foundations in Microbiology Fifth Edition Talaro Chapter 15 The Acquisition of Specific Immunity and Its Applications Chapter 15 2 Chapter Overview 1. Development of the Dual Lymphocyte System 2. Entrance
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,
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
Cell isolation. Spleen and lymph nodes (axillary, inguinal) were removed from mice
Supplementary Methods: Cell isolation. Spleen and lymph nodes (axillary, inguinal) were removed from mice and gently meshed in DMEM containing 10% FBS to prepare for single cell suspensions. CD4 + CD25
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?
Figure S1. Generation of inducible PTEN deficient mice and the BMMCs (A) B6.129 Pten loxp/loxp mice were mated with B6.
Figure S1. Generation of inducible PTEN deficient mice and the BMMCs (A) B6.129 Pten loxp/loxp mice were mated with B6.129-Gt(ROSA)26Sor tm1(cre/ert2)tyj /J mice. To induce deletion of the Pten locus,
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
Erbb2 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
Supplemental materials
Supplemental materials 1 Supplemental Fig. 1 Immunogram This immunogram summarizes patient clinical data and immune parameters at corresponding time points for Patient IMF-32. The top panel illustrates
Supplementary Table 1. Functional avidities of survivin-specific T-cell clones against LML-peptide
Supplementary Table 1. Functional avidities of survivin-specific T-cell clones against LML-peptide pulsed T2 cells. clone avidity by 4-hour 51 Cr-release assay 50% lysis at E:T 10:1 [LML peptide, M] #24
Therapeutic Cancer Vaccines
Therapeutic Cancer Vaccines Goal for all therapeutic cancer vaccines: To enhance the natural immune response so that it becomes an effective therapy Approaches being investigated in clinical studies: Whole
Immunological Tolerance
Immunological Tolerance Introduction Definition: Unresponsiveness to an antigen that is induced by exposure to that antigen Tolerogen = tolerogenic antigen = antigen that induces tolerance Important for
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
MT09 - Normal Human Tissue Microarray, FDA
Reveal Biosciences offers Histochemical Staining, Immunohistochemistry (IHC), In Situ Hybridization (ISH), Whole Slide Imaging, and Quantitative Image Analysis on any TMA MT09 - Normal Human Tissue Microarray,
Supplemental Figure 1. Activated splenocytes upregulate Serpina3g and Serpina3f expression.
Relative Serpin expression 25 2 15 1 5 Serpina3f 1 2 3 4 5 6 8 6 4 2 Serpina3g 1 2 3 4 5 6 C57BL/6 DBA/2 Supplemental Figure 1. Activated splenocytes upregulate Serpina3g and Serpina3f expression. Splenocytes
What is Autoimmunity?
Autoimmunity What is Autoimmunity? Robert Beatty MCB150 Autoimmunity is an immune response to self antigens that results in disease. The immune response to self is a result of a breakdown in immune tolerance.
What is Autoimmunity?
Autoimmunity What is Autoimmunity? Robert Beatty MCB150 Autoimmunity is an immune response to self antigens that results in disease. The immune response to self is a result of a breakdown in immune tolerance.
Adaptive Immunity: Specific Defenses of the Host
17 Adaptive Immunity: Specific Defenses of the Host SLOs Differentiate between innate and adaptive immunity, and humoral and cellular immunity. Define antigen, epitope, and hapten. Explain the function
Supplementary 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
Adaptive Immunity: Humoral Immune Responses
MICR2209 Adaptive Immunity: Humoral Immune Responses Dr Allison Imrie 1 Synopsis: In this lecture we will review the different mechanisms which constitute the humoral immune response, and examine the antibody
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
Anti-Tumor Efficacy of Gene Vaccine Expressing PSMA
6 Clin Oncol Cancer Res () 7: 6-5 DOI.7/s85--5-7 Anti-Tumor Efficacy of Gene Vaccine Expressing PSMA Xiao-ling YANG Jing LV Yue-hong ZHANG Bo NIU, Department of Laboratory Medicine, Shanxi Bo ai Hospital,
Macmillan Publications
S1 S2 S3 S3 S3 S4 S5 S6 S7 S8 S8 S9 S10 S11 S11 S12 S13 S14 S15 S17 S18 S19 Bladder Cancer: Non-Invasive, Invasive and Advanced Bone Cancer: Primary, Secondary Colon Cancer, Anal Cancer, Rectal Cancer
Supporting Information
Supporting Information Valkenburg et al. 10.1073/pnas.1403684111 SI Materials and Methods ELISA and Microneutralization. Sera were treated with Receptor Destroying Enzyme II (RDE II, Accurate) before ELISA
ankylosing spondylitis Department of Clinical Immunology, Xijing Hospital, The Fourth Military
Functional defects in CD4 + CD25 high FoxP3 + regulatory cells in ankylosing spondylitis Huifang Guo 1, 2, 3, Ming Zheng 1, 2, 3, Kui Zhang 1, 3, Fengfan Yang 1, 3, Xin Zhang 1, 3, Qing Han 1, 3, Zhi-Nan
MCB 4211 Basic Immunology 2nd Exam; 10/26/17 Peoplesoft #:
For this first section, circle the letter that precedes the best answer for each of the following multiple-choice questions. LOOK AT ALL ALTERNATIVES BEFORE CHOOSING YOUR ANSWER. 1. The TcR (T cell receptor)
Supplementary Figure 1. Genotyping strategies for Mcm3 +/+, Mcm3 +/Lox and Mcm3 +/- mice and luciferase activity in Mcm3 +/Lox mice. A.
Supplementary Figure 1. Genotyping strategies for Mcm3 +/+, Mcm3 +/Lox and Mcm3 +/- mice and luciferase activity in Mcm3 +/Lox mice. A. Upper part, three-primer PCR strategy at the Mcm3 locus yielding
RAISON D ETRE OF THE IMMUNE SYSTEM:
RAISON D ETRE OF THE IMMUNE SYSTEM: To Distinguish Self from Non-Self Thereby Protecting Us From Our Hostile Environment. Innate Immunity Acquired Immunity Innate immunity: (Antigen nonspecific) defense
The next steps for effective cancer immunotherapy and viral vaccines. Peter Selby FACP(UK)
The next steps for effective cancer immunotherapy and viral vaccines Peter Selby FACP(UK) Richard Alan Steve Sasha Matt Nav Vile Melcher Griffin Zougman Bentham Vasudev Adel Nick Gemma Liz Samson Hornigold
SEVENTH EDITION CHAPTER
Judy Owen Jenni Punt Sharon Stranford Kuby Immunology SEVENTH EDITION CHAPTER 16 Tolerance, Autoimmunity, and Transplantation Copyright 2013 by W. H. Freeman and Company Immune tolerance: history * Some
Significance of the MHC
CHAPTER 7 Major Histocompatibility Complex (MHC) What is is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) Significance of the MHC role in immune response role in organ
Chapter 22: The Lymphatic System and Immunity
Bio40C schedule Lecture Immune system Lab Quiz 2 this week; bring a scantron! Study guide on my website (see lab assignments) Extra credit Critical thinking questions at end of chapters 5 pts/chapter Due
Cancer Vaccines and Cytokines. Elizabeth A. Mittendorf, MD, PhD Assistant Professor Department of Surgical Oncology
Cancer Vaccines and Cytokines Elizabeth A. Mittendorf, MD, PhD Assistant Professor Department of Surgical Oncology Disclosures I serve as the PI on a phase III trial sponsored by Galena BioPharma investigating
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
1. Overview of Adaptive Immunity
Chapter 17A: Adaptive Immunity Part I 1. Overview of Adaptive Immunity 2. T and B Cell Production 3. Antigens & Antigen Presentation 4. Helper T cells 1. Overview of Adaptive Immunity The Nature of Adaptive
Copyright. Tocagen Inc. Lead Product Candidate: Toca 511 & Toca FC Preclinical Overview
Lead Product Candidate: Toca 511 & Toca FC Preclinical Overview Toca 511, delivers CD prodrug activator gene selectively to cancer cells Regulatory genes Structural RRV genes CD gene Regulatory genes Toca
Immunotherapy on the Horizon: Adoptive Cell Therapy
Immunotherapy on the Horizon: Adoptive Cell Therapy Joseph I. Clark, MD, FACP Professor of Medicine Loyola University Chicago Stritch School of Medicine Maywood, IL June 23, 2016 Conflicts of Interest
Supporting Information
Supporting Information Chan et al. 1.173/pnas.9654916 A Patient B Xenograft C * remaining feature of normal lymph node * * * D lymphocytes Infiltrating transitional carcinoma cells E Enlarged axillary
Immune system. Self/non-self recognition. Memory. The state of protection from infectious disease. Acceptance vs rejection
Immune system The state of protection from infectious disease Self/non-self recognition 自我 非我 Acceptance vs rejection Memory 疫苗 2 Microbes Commensal Microbes 共生菌 Normal flora: usually confined to certain
CD44
MR1-5-OP-RU CD24 CD24 CD44 MAIT cells 2.78 11.2 WT RORγt- GFP reporter 1 5 1 4 1 3 2.28 1 5 1 4 1 3 4.8 1.6 8.1 1 5 1 4 1 3 1 5 1 4 1 3 3.7 3.21 8.5 61.7 1 2 1 3 1 4 1 5 TCRβ 2 1 1 3 1 4 1 5 CD44 1 2 GFP
TITLE: Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens
AD AWARD NUMBER: W81XWH-04-1-0668 TITLE: Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens PRINCIPAL INVESTIGATOR: R. Todd Reilly, Ph.D. CONTRACTING ORGANIZATION: Johns Hopkins
[AUTOIMMUNITY] July 14, 2013
![[AUTOIMMUNITY] July 14, 2013](/thumbs/72/66734585.jpg "[AUTOIMMUNITY] July 14, 2013")
This sheet includes only the extra notes. Slide 5,6: [AUTOIMMUNITY] July 14, 2013 Autoimmunity is the condition or case where the immune system is activated by self antigensand when the immune system no
LAG-3: Validation Of Next Generation Checkpoint Pathways
LAG-3: Validation Of Next Generation Checkpoint Pathways Frédéric Triebel, CO/CMO Immune Checkpoint Modulation & Combination Therapies April 13, 2016 London, UK. 1 AX:PRR; NADAQ:PBMD Notice: Forward Looking
New Biological and Immunological Therapies for Cancer
New Biological and Immunological Therapies for Cancer Sant P. Chawla, M.D., FRACP The Sarcoma Oncology Center, Santa Monica CA 90403 7 th International Conference on Drug Discovery &Therapy 1 Promising
Potential Rebalancing of the Immune System by Anti-CD52 Therapy
Potential Rebalancing of the Immune System by Anti-CD52 Therapy Johanne Kaplan, PhD VP Neuroimmunology Research Genzyme March 26, 2013 RESTRICTED USE SEE TRAINING MEMO 2011 DO Genzyme NOT 1COPY Corporation
African American Men and Prostate Cancer Management Option for Clinical PROSPECT Trial Participation in an Immunotherapy Study
African American Men and Prostate Cancer Management Option for Clinical PROSPECT Trial Participation in an Immunotherapy Study Jennifer Harris, PharmD Medical Science Liaison Bavarian Nordic, Inc. Prostate
Nature Immunology: doi: /ni Supplementary Figure 1. Gene expression profile of CD4 + T cells and CTL responses in Bcl6-deficient mice.
Supplementary Figure 1 Gene expression profile of CD4 + T cells and CTL responses in Bcl6-deficient mice. (a) Gene expression profile in the resting CD4 + T cells were analyzed by an Affymetrix microarray
Animal Models to Understand Immunity
Animal Models to Understand Immunity Hussein El Saghire hesaghir@sckcen.be Innate Adaptive immunity Immunity MAPK and NF-kB TLR pathways receptors Fast Slow Non-specific Specific NOD-like receptors T-cell
TITLE: Prostate Derived Ets Factor, an Immunogenic Breast Cancer Antigen. CONTRACTING ORGANIZATION: Roswell Park Cancer Institute Buffalo, NY, 14263
AD Award Number: W81XWH-05-1-0524 TITLE: Prostate Derived Ets Factor, an Immunogenic Breast Cancer Antigen PRINCIPAL INVESTIGATOR: Ashwani Sood, Ph.D. CONTRACTING ORGANIZATION: Roswell Park Cancer Institute
Physiology Unit 3. ADAPTIVE IMMUNITY The Specific Immune Response
Physiology Unit 3 ADAPTIVE IMMUNITY The Specific Immune Response In Physiology Today The Adaptive Arm of the Immune System Specific Immune Response Internal defense against a specific pathogen Acquired
Chapter 17B: Adaptive Immunity Part II
Chapter 17B: Adaptive Immunity Part II 1. Cell-Mediated Immune Response 2. Humoral Immune Response 3. Antibodies 1. The Cell-Mediated Immune Response Basic Steps of Cell-Mediated IR 1 2a CD4 + MHC cl.
MHC class I MHC class II Structure of MHC antigens:
MHC class I MHC class II Structure of MHC antigens: MHC class I antigens consist of a transmembrane heavy chain (α chain) that is non-covalently associated with β2- microglobulin. Membrane proximal domain
Supplemental Figure 1
Supplemental Figure 1 1a 1c PD-1 MFI fold change 6 5 4 3 2 1 IL-1α IL-2 IL-4 IL-6 IL-1 IL-12 IL-13 IL-15 IL-17 IL-18 IL-21 IL-23 IFN-α Mut Human PD-1 promoter SBE-D 5 -GTCTG- -1.2kb SBE-P -CAGAC- -1.kb
The Immune System. These are classified as the Innate and Adaptive Immune Responses. Innate Immunity
The Immune System Biological mechanisms that defend an organism must be 1. triggered by a stimulus upon injury or pathogen attack 2. able to counteract the injury or invasion 3. able to recognise foreign
Doctor of Philosophy
Regulation of Gene Expression of the 25-Hydroxyvitamin D la-hydroxylase (CYP27BI) Promoter: Study of A Transgenic Mouse Model Ivanka Hendrix School of Molecular and Biomedical Science The University of
Cell-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
Dr Olga Pleguezuelos CSO and Project Manager at SEEK
Dr Olga Pleguezuelos CSO and Project Manager at SEEK Imutex Limited, formed in 2016, is a joint venture between SEEK Group and hvivo to accelerate the development of a Mosquito Vaccine (AGS-v) and Broad-
Advances in Cancer Immunotherapy
Advances in Cancer Immunotherapy Immunology 101 for the Non-Immunologist Arnold H. Zea, PhD azea@lsuhsc.edu Disclosures No relevant financial relationships to disclose This presentation does not contain
Multi-normal human tissues, FDA, 96 samples, 35 organs/sites from three individuals (1.5mm)
ab178228 Multi-normal human tissues, FDA, 96 samples, 35 organs/sites from three individuals (1.5mm) Instructions for Use Designed for antibody cross reactivity analysis and IHC or ISH based protein or
BAVARIAN NORDIC BIO DEUTSCHLAND PRESENTATION OCTOBER 2014 CSE/OMX:BAVA, OTC:BVNRY
BAVARIAN NORDIC BIO DEUTSCHLAND PRESENTATION OCTOBER 2014 CSE/OMX:BAVA, OTC:BVNRY This presentation includes "forward-looking statements" that involve risks, uncertainties and other factors, many of which
AMDCC Progress Report Duke/UNC/Stanford Unit. Program Director Thomas M. Coffman, MD
AMDCC Progress Report Duke/UNC/Stanford Unit Program Director Thomas M. Coffman, MD Susceptibility Mutation Model Development + ApoE-/- +STZ Kidney Phenotype Screen Vascular & Kidney Phenotype Screen Generate
COURSE: Medical Microbiology, MBIM 650/720 - Fall TOPIC: Antigen Processing, MHC Restriction, & Role of Thymus Lecture 12
COURSE: Medical Microbiology, MBIM 650/720 - Fall 2008 TOPIC: Antigen Processing, MHC Restriction, & Role of Thymus Lecture 12 FACULTY: Dr. Mayer Office: Bldg. #1, Rm B32 Phone: 733-3281 Email: MAYER@MED.SC.EDU
Overview B cell development T cell development
Topics Overview B cell development T cell development Lymphocyte development overview (Cont) Receptor diversity is produced by gene rearrangement and is random Includes specificities that will bind to
BREAST CANCER d an BREAST SELF EXAM
BREAST CANCER and BREAST SELF EXAM American Cancer Society Statistics: 2009 Invasive breast cancer will be diagnosed in over 192,370 women Carcinoma in situ will be diagnosed in 62,280 women More than
Transgenic Mice and Genetargeting
Transgenic Mice and Genetargeting mice In Biomedical Science Techniques of transgenic and gene-targeting mice are indispensable for analyses of in vivo functions of particular genes and roles of their
Welcome! Here s our agenda for today:
Welcome! Here s our agenda for today: What is ovarian cancer? What causes it? When does genetic testing come in? When are families at risk for ovarian cancer? What are the treatments? 3 things to remember
Adaptive 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,
Prof. Ibtesam Kamel Afifi Professor of Medical Microbiology & Immunology
By Prof. Ibtesam Kamel Afifi Professor of Medical Microbiology & Immunology Lecture objectives: At the end of the lecture you should be able to: Enumerate features that characterize acquired immune response
Jean-Michel Wal, Karine Adel-Patient, Herve Bernard and Stephane Hazebrouck
The BALB/c mouse model of allergy for the assessment of sensitizing properties of proteins and foods and their alteration by environmental conditions Jean-Michel Wal, Karine Adel-Patient, Herve Bernard
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
CELL BIOLOGY - CLUTCH CH THE IMMUNE SYSTEM.
!! www.clutchprep.com CONCEPT: OVERVIEW OF HOST DEFENSES The human body contains three lines of against infectious agents (pathogens) 1. Mechanical and chemical boundaries (part of the innate immune system)
CONTENTS. About the Authors, xv Contributors, xvi Preface and Acknowiedgments, xvii How to Use Your Textbook, xix About the Companion Website, xxiii
Coico, Richard Immunology 2015 About the Authors, xv Contributors, xvi Preface and Acknowiedgments, xvii How to Use Your Textbook, xix About the Companion Website, xxiii 1 OVERVIEW OF THE IMMUNE SYSTEM,
Potential cross reactions between HIV 1 specific T cells and the microbiome. Andrew McMichael Suzanne Campion
Potential cross reactions between HIV 1 specific T cells and the microbiome Andrew McMichael Suzanne Campion Role of the Microbiome? T cell (and B cell) immune responses to HIV and Vaccines are influenced
Supplementary Figure 1. Generation of knockin mice expressing L-selectinN138G. (a) Schematics of the Sellg allele (top), the targeting vector, the
Supplementary Figure 1. Generation of knockin mice expressing L-selectinN138G. (a) Schematics of the Sellg allele (top), the targeting vector, the targeted allele in ES cells, and the mutant allele in
RAISON D ETRE OF THE IMMUNE SYSTEM:
RAISON D ETRE OF THE IMMUNE SYSTEM: To Distinguish Self from Non-Self Thereby Protecting Us From Our Hostile Environment. Innate Immunity Adaptive Immunity Innate immunity: (Antigen - nonspecific) defense
Antigens and Immunogens
Background 1. Medical Importance of Immune System (vaccines, immunodeficiency diseases, hypersensitivity) 2. How the Immune System Works (innate & adaptive immune mech., B/T cells, Abs, Cytokines) 2. Cells
Anti-idiotype and anti-immunoglobulin antibodies are promising biomarkers of early breast cancer
Anti-idiotype and anti-immunoglobulin antibodies are promising biomarkers of early breast cancer Marie-Claire Maroun, Lawrence Grossman, Rooshan Arshad, Leonard Lipovich, and Félix Fernández Madrid Wayne
Current Tumor Immunotherapy
Current Tumor Immunotherapy Part 1: On the preclinical and clinical efficacy of the current cancer vaccines. Part 2: The critical role of cancer vaccines in new integrative approaches. The State of the
Oncology 101. Cancer Basics
Oncology 101 Cancer Basics What Will You Learn? What is Cancer and How Does It Develop? Cancer Diagnosis and Staging Cancer Treatment What is Cancer? Cancer is a group of more than 100 different diseases
gp100 (209-2M) peptide and High Dose Interleukin-2 in HLA-A2+ Advanced Melanoma Patients Cytokine Working Group Experience
gp100 (209-2M) peptide and High Dose Interleukin-2 in HLA-A2+ Advanced Melanoma Patients Cytokine Working Group Experience Metastatic Melanoma- Progress in Past 30 years Approved Therapies (USA) Date DTIC
Helminth worm, Schistosomiasis Trypanosomes, sleeping sickness Pneumocystis carinii. Ringworm fungus HIV Influenza
Helminth worm, Schistosomiasis Trypanosomes, sleeping sickness Pneumocystis carinii Ringworm fungus HIV Influenza Candida Staph aureus Mycobacterium tuberculosis Listeria Salmonella Streptococcus Levels
T Cell Development. Xuefang Cao, MD, PhD. November 3, 2015
T Cell Development Xuefang Cao, MD, PhD November 3, 2015 Thymocytes in the cortex of the thymus Early thymocytes development Positive and negative selection Lineage commitment Exit from the thymus and
Medical Virology Immunology. Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University
Medical Virology Immunology Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University Human blood cells Phases of immune responses Microbe Naïve
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
Cationic Liposome-DNA Complexes as Immunomodulators and Vaccine Adjuvants
Cationic Liposome-DNA Complexes as Immunomodulators and Vaccine Adjuvants September 29, 28 Platform Technology Proprietary Cationic Lipid-DNA Complexes Cationic/Neutral Lipid + DNA = JVRS-1 JVRS-1 + Antigen
STATE 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
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:
Minor H Antigen-Specific T Cells -The Black Box of the GVL Effect
Minor H Antigen-Specific T Cells -The Black Box of the GVL Effect All Allogeneic Stem Cell Transplants Are Blind Doctor Donor Patient Genetic polymorphism gives rise to unique peptides in donor and recipient
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
The Major Histocompatibility Complex (MHC)
The Major Histocompatibility Complex (MHC) An introduction to adaptive immune system before we discuss MHC B cells The main cells of adaptive immune system are: -B cells -T cells B cells: Recognize antigens
New Horizons in radionuclide therapy. John Buscombe Royal Free Hospital
New Horizons in radionuclide therapy John Buscombe Royal Free Hospital Date for you diary Interested in Radionuclide imaging and therapy using antibodies and peptides IRIST 2008 Krakow Poland 18-21 June
Examples 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
ACTR (Antibody Coupled T-cell Receptor): A universal approach to T-cell therapy
ACTR (Antibody Coupled T-cell Receptor): A universal approach to T-cell therapy European Medicines Agency Workshop on Scientific and Regulatory Challenges of Genetically Modified Cell-based Cancer Immunotherapy
International Short Summer Course of the Mouse July 29-31, 2013 At Nanjing University MRAC. The Mouse in the Immunology. Yuichi Obata RIKEN BRC
International Short Summer Course of the Mouse July 29-31, 2013 At Nanjing University MRAC The Mouse in the Immunology Yuichi Obata RIKEN BRC 1 The 1 st Term: 2002~2006 The 2 nd Term: 2007~2011 The 3 rd
Emerging Targets in Immunotherapy
Emerging Targets in Immunotherapy So Jin Shin, M.D. Department of Obstetrics and Gynecology, Keimyung University, School of Medicine, Daegu, Korea no-0ncology Todays is.. ancer Immunotherapy? nd immunotherapy
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
Cytotoxicity assays. Rory D. de Vries, PhD 1. Viroscience lab, Erasmus MC, Rotterdam, the Netherlands
Cytotoxicity assays Rory D. de Vries, PhD 1 1 Viroscience lab, Erasmus MC, Rotterdam, the Netherlands Anti-influenza immunity Humoral / CD4+ / CD8+ / NK? Function of CTL Elimination of virus-infected cells?
all of the above the ability to impart long term memory adaptive immunity all of the above bone marrow none of the above
1. (3 points) Immediately after a pathogen enters the body, it faces the cells and soluble proteins of the innate immune system. Which of the following are characteristics of innate immunity? a. inflammation