Novel RORg Agonists Enhance Anti-Tumor Activity of Adoptive T Cell Therapy
|
|
- Luke Wood
- 6 years ago
- Views:
Transcription
1 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, Richard Bousley, Clarke Taylor, Chad van Huis, Donald Skalitzky, Thomas Aicher, Peter Toogood, Weiping Zou, Gary Glick, Chrystal Paulos, Laura Carter May 2015
2 Type 17 T Cells Mediate Potent, Durable Anti-Tumor Responses Murine Transfer Model Human Transfer Model Ovarian Cancer Patients pmel-1 CD8 T cells + B16F10 Melanoma Th17 + Tc17 Meso CAR-T cells + M108 Tumor Correlation of RORg pathway with improved patient prognosis Blood , Sci Transl Med , 55ra78 Blood ,
3 RORgt is Master Transcription Factor for Type 17 T cells Can RORg agonists be used to enhance Type 17 responses and antitumor T cell responses? Transcription Factor agonist will activate genetic program Multiple mechanisms Not equivalent to overexpressing IL-17
4 Synthetic Agonists Enhance RORg Activity Gal4-RORg Reporter Cell Assay
5 Cytokine (ng/ml) RORg Agonists Enhance Cytokine Production by Murine Th17 and Tc17 Polarized T Cells CD4 T Cells Th17 conditions CD8 T Cells Tc17 conditions IL-17A IL-17F IL-22 GMCSF OT-I or OT-II splenocytes activated 4 days with peptide, IL-6, TGFb
6 % Cells RORg Agonists Enhance Cytokine Production by Unpolarized Murine T Cells Th0 Condition (IL-2) RORg-dependent Effect IL-17A IFNg IL17A DMSO Agonist DMSO Agonist 5 IL-17A Production from Th0 vs Th17 Cells 0 WT RORg (-/-) DMSO Agonist DMSO Agonist Trp-1 splenocytes activated 5 days with peptide B6 splenocytes activated 4 days with anti-cd3/cd28, IL-6, TGFb
7 % Change from DMSO RORg Agonists Shift the Balance of Co-stimulation over Co-inhibition PD1 CD160 CD73 CD27 CD28 CTLA4 PD1 TIGIT CD160 LAIR1 CD73 CD226 CD27 CD137 CD28 IL17A B6 splenocytes activated 4-5 days with anti-cd3/cd28, IL-6, TGFb +/- agonist flow cytometry, qpcr
8 RORg Agonists Desensitize Cells to PD-1 Checkpoint Inhibition RORg agonist Decreases PD-1 Expression and Percentage PD-1+ Cells RORg Agonist Desensitizes Cells to PD-L1 Inhibition of Proliferation 2º Stimulation (anti-cd3) Similar restoration of cytokine production observed (IL-17, IFNg) OT-I splenocytes activated 4 days with peptide, IL-6, TGFb +/-agonist; washed, rested then restimulated for 6 days
9 EG7 Tumor Growth is Inhibited Following Adoptive Transfer of RORg Agonist Treated Tc17 Cells Significant inhibition of tumor growth and improved survival
10 Adoptive Cell Therapy Model pmel-1 CD8 or TRP-1 CD4 + T cells n (1e6) IL-2 IL-6, TGF-b, IL-21, IL-1B Anti-IFN/4 Th0 Th17 B16F10 *most challenging line of melanoma to treat. Treat post 10 days of development Dr Chrystal Paulos, Dr Kinga Majchrzak Medical University of South Carolina
11 Percent survival Tumor Volume (mm2) RORg Agonist Improves Effectiveness of Transferred T Cells vs Established B16F10 Tumors Trp-1 CD4 Th17 cells PMEL-1 CD8 Tc17 cells Trp-1 CD4 Th0 cells No Cells Th17 Th17 + Agonist Days No Cells Tc17 Tc17 + Agonist Days No Cells Th0 Th0 + Agonist Days Days Days Days Dr Chrystal Paulos, Dr Kinga Majchrzak Medical University of South Carolina
12 Percent survival Tumor Volume (mm2) % type 17 in the tumor RORg Agonist Improves Effectiveness of co-transferred CD4+ CD8+ T Cells vs Established B16F10 Tumors Trp-1 Th17 + pmel-1 Tc17 Tumor-specific TIL Day No Cells Th17 + Tc17 Th17 + Tc17 + Agonist Days 1 0 Th17 Tc17 Enhanced persistence of agonist treated cells in tumor draining lymph node and spleen Days Dr Chrystal Paulos, Dr Kinga Majchrzak Medical University of South Carolina
13 RORg Agonist Treated Cells Maintain Enhanced Cytokine Production 71 Days After Transfer Splenocytes (day 71) ex vivo Trp-1 Stimulation of CD4 T cells Similar data observed for IL-2 and IL-21 and for pmel-1 CD8 T cells Dr Chrystal Paulos, Dr Kinga Majchrzak Medical University of South Carolina
14 Increased PD-1-Negative TILs in Mice Receiving Agonist Treated Th17 + Tc17 Cells Trp-1 CD4 pmel-1 CD8 Th17 + Tc17 Day 71 Th17 + Tc17 +Agonist Dr Chrystal Paulos, Dr Kinga Majchrzak Medical University of South Carolina
15 Systemic Administration of RORg Agonist Effective Against Established MC38 Colon Carcinoma Inject tumor cells (SC) 3-7 days Begin daily days dosing Tumor Volume Tumor Growth Control Improved Survival Increased plasma cytokines agonist
16 RORg Agonists Increase production of pro-inflammatory cytokines and chemokines Increase co-stimulatory and decrease co-inhibitory receptor expression Desensitize cells to PD-L1-medidated inhibition Decrease Treg development Addition of RORg agonists to in vitro T cell expansion cultures significantly enhances anti-tumor responses Effective in CD4 and CD8 model systems Effective with Type17 cytokine cocktails or IL-2 Observe long-lasting effects consistent with RORg biology
17 Thank You! Jacques Moisan Xiao Hu Rodney Morgan Xikui Liu Kellie Demock Yahong Wang Charles Lesch Brian Sanchez Richard Bousley Clarke Taylor Chad van Huis Donald Skalitzky Thomas Aicher Peter Toogood Gary Glick Medical University of South Carolina Kinga Majchrzak Chrystal Paulos University of Michigan Weiping Zou
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
More informationEnhancing 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
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 informationRestoring 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
More informationSupplementary Fig. 1 p38 MAPK negatively regulates DC differentiation. (a) Western blot analysis of p38 isoform expression in BM cells, immature DCs
Supplementary Fig. 1 p38 MAPK negatively regulates DC differentiation. (a) Western blot analysis of p38 isoform expression in BM cells, immature DCs (idcs) and mature DCs (mdcs). A myeloma cell line expressing
More informationSupplementary Figure 1. Deletion of Smad3 prevents B16F10 melanoma invasion and metastasis in a mouse s.c. tumor model.
A B16F1 s.c. Lung LN Distant lymph nodes Colon B B16F1 s.c. Supplementary Figure 1. Deletion of Smad3 prevents B16F1 melanoma invasion and metastasis in a mouse s.c. tumor model. Highly invasive growth
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 informationSupplementary Figures
Supplementary Figures Supplementary Fig. 1. Surface thiol groups and reduction of activated T cells. (a) Activated CD8 + T-cells have high expression levels of free thiol groups on cell surface proteins.
More informationSupplementary Figure 1 IL-27 IL
Tim-3 Supplementary Figure 1 Tc0 49.5 0.6 Tc1 63.5 0.84 Un 49.8 0.16 35.5 0.16 10 4 61.2 5.53 10 3 64.5 5.66 10 2 10 1 10 0 31 2.22 10 0 10 1 10 2 10 3 10 4 IL-10 28.2 1.69 IL-27 Supplementary Figure 1.
More informationb-catenin and PI3Kd inhibition expands precursor Th17 cells with heightened stemness and antitumor activity
b-catenin and PI3Kd inhibition expands precursor Th17 cells with heightened stemness and antitumor activity Kinga Majchrzak,, Sherine S.L. Chan, Chrystal M. Paulos JCI Insight. 2017;2(8):e90547.. Research
More informationSupplemental 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
More informationSupplemental 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
More informationEnhanced 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
More informationSupplementary Table 1 Clinicopathological characteristics of 35 patients with CRCs
Supplementary Table Clinicopathological characteristics of 35 patients with CRCs Characteristics Type-A CRC Type-B CRC P value Sex Male / Female 9 / / 8.5 Age (years) Median (range) 6. (9 86) 6.5 (9 76).95
More informationTim-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
More informationECM1 controls T H 2 cell egress from lymph nodes through re-expression of S1P 1
ZH, Li et al, page 1 ECM1 controls T H 2 cell egress from lymph nodes through re-expression of S1P 1 Zhenhu Li 1,4,Yuan Zhang 1,4, Zhiduo Liu 1, Xiaodong Wu 1, Yuhan Zheng 1, Zhiyun Tao 1, Kairui Mao 1,
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 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 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 informationTumor Immunology: A Primer
Transcript Details This is a transcript of a continuing medical education (CME) activity accessible on the ReachMD network. Additional media formats for the activity and full activity details (including
More 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 informationSupplementary Figure 1. mrna expression of chitinase and chitinase-like protein in splenic immune cells. Each splenic immune cell population was
Supplementary Figure 1. mrna expression of chitinase and chitinase-like protein in splenic immune cells. Each splenic immune cell population was sorted by FACS. Surface markers for sorting were CD11c +
More informationCancer 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
More informationEvidence for Systemic Effects Moves PV-10 Toward Further Clinical Trials
PV-10 Moves Forward-1 Evidence for Systemic Effects Moves PV-10 Toward Further Clinical Trials At the same time that current research projects are solidifying and reinforcing the evidence for PV-10 s systemic
More informationRadiation Therapy as an Immunomodulator
Radiation Therapy as an Immunomodulator Yvonne Mowery, MD, PhD February 20, 2017 Tumor/Immune System Balance Kalbasi, JCI 2013 UNC-Duke-NC State-Wake Forest Spring 2017 2 RT Can Shift Balance Toward Elimination
More informationCORRECTION NOTICE. Nat. Chem. Biol. 11, (2015) Sterol metabolism controls T H 17 differentiation by generating endogenous RORγ agonists
CORRECTION NOTICE Nat. Chem. Biol. 11, 141 147 (2015) Sterol metabolism controls T H 17 differentiation by generating endogenous RORγ agonists Xiao Hu, Yahong Wang, Ling-Yang Hao, Xikui Liu, Chuck A Lesch,
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 information2/16/2018. The Immune System and Cancer. Fatal Melanoma Transferred in a Donated Kidney 16 years after Melanoma Surgery
C007: Immunology of Melanoma: Mechanisms of Immune Therapies Delphine J. Lee, MD, PhD Chief and Program Director, Dermatology, Harbor UCLA Medical Center Principal Investigator, Los Angeles Biomedical
More informationSupplemental Materials for. Effects of sphingosine-1-phosphate receptor 1 phosphorylation in response to. FTY720 during neuroinflammation
Supplemental Materials for Effects of sphingosine-1-phosphate receptor 1 phosphorylation in response to FTY7 during neuroinflammation This file includes: Supplemental Table 1. EAE clinical parameters of
More informationSupplementary Information:
Supplementary Information: Follicular regulatory T cells with Bcl6 expression suppress germinal center reactions by Yeonseok Chung, Shinya Tanaka, Fuliang Chu, Roza Nurieva, Gustavo J. Martinez, Seema
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 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 informationNature Medicine: doi: /nm.3922
Title: Glucocorticoid-induced tumor necrosis factor receptor-related protein co-stimulation facilitates tumor regression by inducing IL-9-producing helper T cells Authors: Il-Kyu Kim, Byung-Seok Kim, Choong-Hyun
More informationPREPARED 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
More informationUnderstanding the T cell response to tumors using transnuclear mouse models
Understanding the T cell response to tumors using transnuclear mouse models Stephanie Dougan Dana-Farber Cancer Institute Boston, MA Presenter Disclosure Information Stephanie Dougan The following relationships
More informationTargeting tumour associated macrophages in anti-cancer therapies. Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018
Targeting tumour associated macrophages in anti-cancer therapies Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018 Macrophages: Professional phagocytes of the myeloid lineage APC,
More informationDendritic 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
More informationEngineered T cells: Next-generation cancer immunotherapy
Engineered T cells: Next-generation cancer immunotherapy Rahul Purwar, Assistant Professor Department of Biosciences & Bioengineering Indian Institute of Technology Bombay (IIT Bombay) Mumbai, India, 400076
More informationSelective IDO1 Inhibition: Pharmacodynamic and Antitumor Activity of INCB Holly K. Koblish Incyte Corporation
Selective IDO1 Inhibition: Pharmacodynamic and Antitumor Activity of INCB24360 Holly K. Koblish Incyte Corporation Presenter Disclosure Information The following relationships exist related to this presentation:
More informationInterferon-dependent IL-10 production by Tregs limits tumor Th17 inflammation
Interferon-dependent IL-10 production by Tregs limits tumor Th17 inflammation C. Andrew Stewart,, Werner Müller, Giorgio Trinchieri J Clin Invest. 2013;123(11):4859-4874. https://doi.org/10.1172/jci65180.
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 informationSpleen. mlns. E Spleen 4.1. mlns. Spleen. mlns. Mock 17. Mock CD8 HIV-1 CD38 HLA-DR. Ki67. Spleen. Spleen. mlns. Cheng et al. Fig.
C D E F Mock 17 Mock 4.1 CD38 57 CD8 23.7 HLA-DR Ki67 G H I Cheng et al. Fig.S1 Supplementary Figure 1. persistent infection leads to human T cell depletion and hyper-immune activation. Humanized mice
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 informationAccepted 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:
More informationSupplementary 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
More informationDeveloping Novel Immunotherapeutic Cancer Treatments for Clinical Use
Developing Novel Immunotherapeutic Cancer Treatments for Clinical Use Oncology for Scientists March 8 th, 2016 Jason Muhitch, PhD Assistant Professor Department of Urology Email: jason.muhitch@roswellpark.org
More informationImmunotherapy for the Treatment of Cancer
Immunotherapy for the Treatment of Cancer Jason Muhitch, PhD Assistant Professor Department of Urology Department of Immunology Roswell Park Comprehensive Cancer Center Oncology for Scientists March 15,
More informationBASIC MECHANISM OF TUMOR IMMUNE SUPPRESSION
BASIC MECHANISM OF TUMOR IMMUNE SUPPRESSION Zihai Li, M.D., Ph.D. Leader, Cancer Immunology Program Hollings Cancer Center Medical University of South Carolina (MUSC) DISCLOSURE GOALS Understand that immune
More informationNKTR-214 plus NKTR-262, a Scientifically-Guided Rational Combination Approach for Immune Oncology
plus NKTR-262, a Scientifically-Guided Rational Combination Approach for Immune Oncology Jonathan Zalevsky SVP, Biology and Preclinical Development Nektar Therapeutics World Preclinical Congress, 2017
More informationTumors arise from accumulated genetic mutations. Tumor Immunology (Cancer)
Tumor Immunology (Cancer) Tumors arise from accumulated genetic mutations Robert Beatty MCB150 Mutations Usually have >6 mutations in both activation/growth factors and tumor suppressor genes. Types of
More informationSupplemental 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,
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 informationRationale and results from. BRAFi and immunotherapy
Rationale and results from emerging combinations of BRAFi and immunotherapy Antoni Ribas, M.D. rofessor of Medicine rofessor of Surgery rofessor of Molecular and Medical harmacology Director, Tumor Immunology
More informationImmuno-Oncology Clinical Trials Update: Therapeutic Anti-Cancer Vaccines Issue 7 April 2017
Delivering a Competitive Intelligence Advantage Immuno-Oncology Clinical Trials Update: Therapeutic Anti-Cancer Vaccines Issue 7 April 2017 Immuno-Oncology CLINICAL TRIALS UPDATE The goal of this MONTHLY
More informationInternational 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
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 informationA fresh approach to Immuno-oncology: Ex vivo analysis of drug efficacy in fresh patient tumortissue
A fresh approach to Immuno-oncology: Ex vivo analysis of drug efficacy in fresh patient tumortissue Soner Altiok, MD, PhD Chief Scientific Officer Nilogen Oncosystems Tampa, Florida - Nilogen Oncosystems,
More informationAdaptive (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,
More informationNK cell flow cytometric assay In vivo DC viability and migration assay
NK cell flow cytometric assay 6 NK cells were purified, by negative selection with the NK Cell Isolation Kit (Miltenyi iotec), from spleen and lymph nodes of 6 RAG1KO mice, injected the day before with
More informationSupplementary Figure 1. Efficient DC depletion in CD11c.DOG transgenic mice
Supplementary Figure 1. Efficient DC depletion in CD11c.DOG transgenic mice (a) CD11c.DOG transgenic mice (tg) were treated with 8 ng/g body weight (b.w.) diphtheria toxin (DT) i.p. on day -1 and every
More informationSynergistic effects of indoleamine 2,3-dioxygenase (IDO) inhibitor drugs and chemotherapy in melanoma.
Synergistic effects of indoleamine 2,3-dioxygenase (IDO) inhibitor drugs and chemotherapy in melanoma. Madhav D. Sharma Cancer Immunology, Inflammation, and Tolerance Program, Department of Pediatrics,
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 informationSupplemental Information. Checkpoint Blockade Immunotherapy. Induces Dynamic Changes. in PD-1 CD8 + Tumor-Infiltrating T Cells
Immunity, Volume 50 Supplemental Information Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1 CD8 + Tumor-Infiltrating T Cells Sema Kurtulus, Asaf Madi, Giulia Escobar, Max Klapholz, Jackson
More informationBlocking 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
More informationDepletion 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
More informationPeer review correspondence
Highly polarized Th17 cells induce EAE via a T-bet-independent mechanism Heather M. Grifka-Walk, Stephen J. Lalor and Benjamin M. Segal Corresponding author: Benjamin Segal, Holtom-Garrett Program in Neuroimmunology
More informationReleasing the Brakes on Tumor Immunity: Immune Checkpoint Blockade Strategies
Releasing the Brakes on Tumor Immunity: Immune Checkpoint Blockade Strategies Jason Muhitch, PhD MIR 509 October 1 st, 2014 Email: jason.muhitch@roswellpark.org 0 Holy Grail of Tumor Immunity Exquisite
More informationDual Targeting Nanoparticle Stimulates the Immune
Dual Targeting Nanoparticle Stimulates the Immune System to Inhibit Tumor Growth Alyssa K. Kosmides, John-William Sidhom, Andrew Fraser, Catherine A. Bessell, Jonathan P. Schneck * Supplemental Figure
More informationEvaluation of an Agonist Anti-CD27 Human Antibody (Varlilumab) and its Potential for Combination With Checkpoint Inhibitors
Evaluation of an Agonist Anti-CD27 Human Antibody (Varlilumab) and its Potential for Combination With Checkpoint Inhibitors Tibor Keler, PhD Chief Scientific Officer Enhancing immunity with immune modulating
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 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 informationAn epithelial-to-mesenchymal transition-inducing potential of. granulocyte macrophage colony-stimulating factor in colon. cancer
An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer Yaqiong Chen, Zhi Zhao, Yu Chen, Zhonglin Lv, Xin Ding, Renxi Wang, He Xiao,
More informationPosters 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
More informationNature 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
More informationW/T Itgam -/- F4/80 CD115. F4/80 hi CD115 + F4/80 + CD115 +
F4/8 % in the peritoneal lavage 6 4 2 p=.15 n.s p=.76 CD115 F4/8 hi CD115 + F4/8 + CD115 + F4/8 hi CD115 + F4/8 + CD115 + MHCII MHCII Supplementary Figure S1. CD11b deficiency affects the cellular responses
More informationCytokine therapy reverses NK cell anergy in MHC-deficient tumors
The Journal of Clinical Investigation Research article Cytokine therapy reverses NK cell anergy in MHC-deficient tumors Michele Ardolino, 1 Camillia S. Azimi, 1 Alexandre Iannello, 1 Troy N. Trevino, 1
More informationCANCER IMMUNOTHERAPY. Cancer Research Center, Dpt. of Medicine & Service of Cytometry University of Salamanca. IBSAL
FARMAFORUM 2015 FACULTAD FARMACIA CANCER IMMUNOTHERAPY Cancer Research Center, Dpt. of Medicine & Service of Cytometry University of Salamanca. IBSAL The immune response to tumors Oncogenic event The immune
More informationTargeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy
Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy Paul A. Beavis,, Michael H. Kershaw, Phillip K. Darcy J Clin Invest. 2017;127(3):929-941. https://doi.org/10.1172/jci89455.
More informationSupplementary Figure 1. Normal T lymphocyte populations in Dapk -/- mice. (a) Normal thymic development in Dapk -/- mice. Thymocytes from WT and Dapk
Supplementary Figure 1. Normal T lymphocyte populations in Dapk -/- mice. (a) Normal thymic development in Dapk -/- mice. Thymocytes from WT and Dapk -/- mice were stained for expression of CD4 and CD8.
More information5% of patients with genetic immunodeficiency develop a cancer during their lifetime (200x)
Immune surveillance 5% of patients with genetic immunodeficiency develop a cancer during their lifetime (200x) Transplanted patients following an immunosuppressor therapy are 80 times more likely to develop
More informationSimultaneous correlation of cytokine production with Treg and Th17 cell proliferation
Simultaneous correlation of cytokine production with Treg and Th17 cell proliferation Jurg Rohrer, PhD Director, R&D BD Biosciences 23-11773-00 For Research Use Only. Not for use in diagnostic or therapeutic
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 informationSUPPLEMENTARY 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
More informationManipulating the Tumor Environment
Manipulating the Tumor Environment Vincenzo Bronte Verona University Hospital vincenzo.bronte@univr.it Escape from immune control can be viewed as one of the «Hallmarks of Cancer» D. Hanahan and R. A.
More informationUnderstanding and overcoming immunoregulatory barriers within
Understanding and overcoming immunoregulatory barriers within the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D. Professor, Departments of Pathology and Medicine Program Leader, Immunology and
More informationIMMUNOTOOLS: EFFECT OF NOTCH-DEFICIENT MACROPHAGES TO AUTOIMMUNE DISEASE WIPAWEE WONGCHANA
IMMUNOTOOLS: EFFECT OF NOTCH-DEFICIENT MACROPHAGES TO AUTOIMMUNE DISEASE 22-02-2017 WIPAWEE WONGCHANA WHAT DO YOU SEE? Allergy Ref: http://carrington.edu/blog/medical/vaccines/smallpox-andsmallpox-vaccine/
More informationAntitumor Activity of CUDC-305, a Novel Oral HSP90 Inhibitor, in Solid and Hematological Tumor Xenograft Models
Antitumor Activity of CUDC-5, a Novel Oral HSP Inhibitor, in Solid and Hematological Tumor Xenograft Models Rudi Bao, MD/PhD April 1, 2 AACR 1th Annual Meeting 2 Experimental and Molecular Therapeutics
More informationMATERIALS AND METHODS. Neutralizing antibodies specific to mouse Dll1, Dll4, J1 and J2 were prepared as described. 1,2 All
MATERIALS AND METHODS Antibodies (Abs), flow cytometry analysis and cell lines Neutralizing antibodies specific to mouse Dll1, Dll4, J1 and J2 were prepared as described. 1,2 All other antibodies used
More informationIdentification of novel immune regulators of tumor growth using highthroughput
Identification of novel immune regulators of tumor growth using highthroughput screening in vivo Tom Brennan 1 Five Prime s Unique Platform Tests Nearly Every Extracellular Protein to Identify Protein
More informationSupplementary. presence of the. (c) mrna expression. Error. in naive or
Figure 1. (a) Naive CD4 + T cells were activated in the presence of the indicated cytokines for 3 days. Enpp2 mrna expression was measured by qrt-pcrhr, infected with (b, c) Naive CD4 + T cells were activated
More informationCancer 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
More informationNature 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
More informationAdvances 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
More informationEnhanced cancer vaccine effectiveness with NKTR-214, a CD122 biased cytokine
SMi Immuno-Oncology, London Loui Madakamutil, Ph. D Vice President, Head for Discovery Enhanced cancer vaccine effectiveness with NKTR-214, a CD122 biased cytokine Sept 26-27 2018 Nektar Therapeutics San
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 informationT cell receptor transgenic lymphocytes infiltrating murine tumors are not induced to express foxp3
JOURNAL OF HEMATOLOGY & ONCOLOGY RESEARCH Open Access T cell receptor transgenic lymphocytes infiltrating murine tumors are not induced to express foxp3 Jon G Quatromoni 1, Lilah F Morris 1, Timothy R
More informationRichard S. Kornbluth, M.D., Ph.D.
Treatment of established tumors with peritumoral injections of CD40 ligand (CD40L), CpG, poly(i:c), and extracellular ATP in murine models Richard S. Kornbluth, M.D., Ph.D. Disclosure: Richard Kornbluth
More informationRaising the bar: optimizing combinations of targeted therapy and immunotherapy
Editorial Page 1 of 5 Raising the bar: optimizing combinations of targeted therapy and immunotherapy Alexandre Reuben 1, Jacob Austin-Breneman 1, Jennifer A. Wargo 1,2 *, Zachary A. Cooper 1,2 * 1 Department
More informationOutline. Case studies & Tumor Immunology platform overview. In vitro assay panel. In vivo models. Clinical and pre-clinical sample analyses
Immuno-Oncology May, 217 Outline Case studies & Tumor Immunology platform overview In vitro assay panel In vivo models Ex vivo analyses Clinical and pre-clinical sample analyses 2 Case 1: an IS Project
More informationHuman Immune System (HIS) mouse models for translational research. Barbara Joyce-Shaikh
Human Immune System (HIS) mouse models for translational research Barbara Joyce-Shaikh Humanized Immune System (HIS) Mouse Models Goals Enable clinically relevant in vivo studies of human cells, tissues,
More information