CA2678353A1 - A method for enhancing t cell response - Google Patents

A method for enhancing t cell response Download PDF

Info

Publication number
CA2678353A1
CA2678353A1 CA002678353A CA2678353A CA2678353A1 CA 2678353 A1 CA2678353 A1 CA 2678353A1 CA 002678353 A CA002678353 A CA 002678353A CA 2678353 A CA2678353 A CA 2678353A CA 2678353 A1 CA2678353 A1 CA 2678353A1
Authority
CA
Canada
Prior art keywords
dose
cell
doses
antigen
immunogenic composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA002678353A
Other languages
English (en)
French (fr)
Inventor
Thomas Kundig
Adrian Bot
Kent Andrew Smith
Zhiyong Qiu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mannkind Corp
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2678353A1 publication Critical patent/CA2678353A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/19—Dendritic cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
    • A61K40/24—Antigen-presenting cells [APC]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/32—T-cell receptors [TCR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/34—Antigenic peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/46—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5152—Tumor cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55516—Proteins; Peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55522—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55577—Saponins; Quil A; QS21; ISCOMS
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Virology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
CA002678353A 2007-02-15 2008-02-15 A method for enhancing t cell response Abandoned CA2678353A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US90198007P 2007-02-15 2007-02-15
US60/901,980 2007-02-15
PCT/US2008/002044 WO2008100598A2 (en) 2007-02-15 2008-02-15 A method for enhancing t cell response

Publications (1)

Publication Number Publication Date
CA2678353A1 true CA2678353A1 (en) 2008-08-21

Family

ID=39690701

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002678353A Abandoned CA2678353A1 (en) 2007-02-15 2008-02-15 A method for enhancing t cell response

Country Status (9)

Country Link
US (1) US20080199485A1 (enExample)
EP (2) EP2481418A1 (enExample)
JP (2) JP5755839B2 (enExample)
CN (2) CN101657213B (enExample)
AU (1) AU2008216669B2 (enExample)
CA (1) CA2678353A1 (enExample)
ES (1) ES2527412T3 (enExample)
MX (1) MX2009008620A (enExample)
WO (1) WO2008100598A2 (enExample)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6977074B2 (en) 1997-07-10 2005-12-20 Mannkind Corporation Method of inducing a CTL response
EP2385059A3 (en) * 2005-06-17 2012-02-15 Mannkind Corporation Methods and compositions to elicit multivalent immune responses against dominant and subdominant epitopes, expressed on cancer cells and tumor stroma
CA2682580A1 (en) 2007-03-30 2008-10-09 Duke University A method of modulating the activity of a nucleic acid molecule
US8728465B2 (en) * 2008-06-17 2014-05-20 Cedars-Sinai Medical Center Use of toll-like receptor ligands as adjuvants to vaccination therapy for brain tumors
DE102008061522A1 (de) * 2008-12-10 2010-06-17 Biontech Ag Verwendung von Flt3-Ligand zur Verstärkung von Immunreaktionen bei RNA-Immunisierung
WO2010075525A1 (en) * 2008-12-24 2010-07-01 Cedars-Sinai Medical Center Method of using tumor cell debris to reduce brain tumor recurrence or growth
IN2012DN02345A (enExample) * 2009-09-16 2015-08-21 Univ Duke
EP2490713A2 (en) 2009-10-23 2012-08-29 MannKind Corporation Cancer immunotherapy and method of treatment
US20130108661A1 (en) 2010-02-05 2013-05-02 Mount Sinai School Of Medicine Methods and compositions for cancer immunotherapy using flagellin-tumor associated antigen fusion protein expressing tumor cells
SG11201504558TA (en) 2012-12-11 2015-07-30 Einstein Coll Med Methods for high throughput receptor:ligand identification
US20150037374A1 (en) * 2013-07-31 2015-02-05 Csl Limited Anti-tumor compositions and uses thereof
WO2015161094A1 (en) 2014-04-16 2015-10-22 Duke University Electrospun cationic nanofibers and methods of making and using the same
HK1249052A1 (zh) 2015-03-06 2018-10-26 BeyondSpring Pharmaceuticals Inc. 治疗与ras突变相关的癌症的方法
WO2016180467A1 (en) * 2015-05-11 2016-11-17 Biontech Cell & Gene Therapies Gmbh Enhancing the effect of car-engineered t cells by means of nucleic acid vaccination
EP3294324A1 (en) 2015-05-13 2018-03-21 Agenus Inc. Vaccines for treatment and prevention of cancer
EP3334726B1 (en) 2015-07-13 2022-03-16 Beyondspring Pharmaceuticals, Inc. Plinabulin compositions
US12514872B2 (en) 2015-11-04 2026-01-06 Duke University Polycationic polymers for use in treating and detecting cancer
US10912748B2 (en) 2016-02-08 2021-02-09 Beyondspring Pharmaceuticals, Inc. Compositions containing tucaresol or its analogs
IL262606B2 (en) 2016-05-18 2023-04-01 Albert Einstein College Medicine Inc pd-l1 variant polypeptides, T-cell modulatory multimeric polypeptides, and methods of using them
SG11201808552XA (en) 2016-05-18 2018-10-30 Cue Biopharma Inc T-cell modulatory multimeric polypeptides and methods of use thereof
CN109475524A (zh) 2016-06-06 2019-03-15 万春药业公司 用于减少中性粒细胞减少症的组合物和方法
US12447464B2 (en) 2016-12-22 2025-10-21 Duke University Polycationic microfibers and methods of using the same
CN110325205B (zh) 2016-12-22 2023-08-15 库尔生物制药有限公司 T细胞调节性多聚体多肽及其使用方法
EP3564386B1 (en) 2016-12-27 2021-12-08 Chugai Seiyaku Kabushiki Kaisha Method for evaluating immunogenicity of test substance
WO2018129381A1 (en) 2017-01-06 2018-07-12 Beyondspring Pharmaceuticals, Inc. Tubulin binding compounds and therapeutic use thereof
US11851471B2 (en) 2017-01-09 2023-12-26 Cue Biopharma, Inc. T-cell modulatory multimeric polypeptides and methods of use thereof
KR20190109479A (ko) 2017-02-01 2019-09-25 비욘드스프링 파마수티컬스, 인코포레이티드. 호중구감소증의 감소 방법
KR20240005989A (ko) 2017-03-15 2024-01-12 큐 바이오파마, 인크. 면역 반응을 조절하는 방법
WO2019139896A1 (en) 2018-01-09 2019-07-18 Cue Biopharma, Inc. Multimeric t-cell modulatory polypeptides and methods of use thereof
WO2019147615A1 (en) 2018-01-24 2019-08-01 Beyondspring Pharmaceuticals, Inc. Composition and method for reducing thrombocytopenia via the administration of plinabulin
EP3784688A2 (en) 2018-04-26 2021-03-03 Agenus Inc. Heat shock protein-binding peptide compositions and methods of use thereof
CN111135310B (zh) * 2019-12-24 2021-05-07 江苏省人民医院(南京医科大学第一附属医院) 一种定制化t细胞表位疫苗的双靶向纳米药、其制备方法及应用
IL296209A (en) 2020-05-12 2022-11-01 Cue Biopharma Inc Multimeric t-cell modulatory polypeptides and methods of using them
JP2023541366A (ja) 2020-09-09 2023-10-02 キュー バイオファーマ, インコーポレイテッド 1型真性糖尿病(t1d)を治療するためのmhcクラスii t細胞調節多量体ポリペプチド及びその使用方法
EP4319751A4 (en) 2021-04-09 2025-02-26 Beyondspring Pharmaceuticals, Inc. THERAPEUTIC COMPOSITIONS AND METHODS FOR THE TREATING OF TUMORS
CN116262779A (zh) * 2021-12-14 2023-06-16 深圳先进技术研究院 一种单细胞筛选鉴定人乳头瘤病毒特异性tcr的方法

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4778879A (en) * 1982-04-20 1988-10-18 Sloan-Kettering Institute For Cancer Research Highly purified human interleukin 2 and method
DE4143467C2 (de) 1991-05-17 1995-02-09 Max Planck Gesellschaft Peptidmotiv und dessen Verwendung
US6037135A (en) * 1992-08-07 2000-03-14 Epimmune Inc. Methods for making HLA binding peptides and their uses
DE4423392A1 (de) 1994-07-04 1996-01-11 Birsner & Grob Biotech Gmbh Verfahren zur Identifizierung antigener Peptide
WO1996027008A2 (de) 1995-02-28 1996-09-06 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., Berlin Mittel zur therapie von tumoren und anderen hyperplasien
US5698396A (en) 1995-06-07 1997-12-16 Ludwig Institute For Cancer Research Method for identifying auto-immunoreactive substances from a subject
CN1221349A (zh) * 1996-06-12 1999-06-30 郭亚军 细胞疫苗、免疫治疗以及它们的制备方法
ES2265165T3 (es) 1997-07-10 2007-02-01 Mannkind Corporation Dispositivo para inducir una respuesta ltc.
US6994851B1 (en) * 1997-07-10 2006-02-07 Mannkind Corporation Method of inducing a CTL response
US6977074B2 (en) 1997-07-10 2005-12-20 Mannkind Corporation Method of inducing a CTL response
US6709844B1 (en) 2000-11-16 2004-03-23 Mannkind Corporation Avoidance of undesirable replication intermediates in plasmid propagation
US20030138808A1 (en) 1998-02-19 2003-07-24 Simard John J.L. Expression vectors encoding epitopes of target-associated antigens
AU749749B2 (en) * 1998-03-16 2002-07-04 Alk-Abello A/S Mutant recombinant allergens
US6861234B1 (en) * 2000-04-28 2005-03-01 Mannkind Corporation Method of epitope discovery
US20030215425A1 (en) 2001-12-07 2003-11-20 Simard John J. L. Epitope synchronization in antigen presenting cells
US20020165176A1 (en) * 2000-05-01 2002-11-07 Haynes Joel R. Nucleic acid immunization
GB0023008D0 (en) * 2000-09-20 2000-11-01 Glaxo Group Ltd Improvements in vaccination
WO2002069907A2 (en) 2001-03-07 2002-09-12 Mannkind Corporation Anti-neovasculature preparations for cancer
WO2003008537A2 (en) * 2001-04-06 2003-01-30 Mannkind Corporation Epitope sequences
MXPA04005382A (es) 2001-11-07 2005-02-24 Mannkind Corp Vectores de expresion que codifican epitopes de antigenos asociados al objetivo y metodos para su diseno.
NZ519363A (en) * 2002-06-05 2004-02-27 Agres Ltd A novel drug dosing regimen
EP1545610A4 (en) * 2002-09-06 2006-11-08 Mannkind Corp EPITOPE SEQUENCES
JP5127224B2 (ja) 2003-06-17 2013-01-23 マンカインド コーポレイション 予防又は治療目的のためのmhcクラスi拘束性エピトープに対する免疫応答を誘発し、増強し、維持する方法
US20050118186A1 (en) 2003-06-17 2005-06-02 Chih-Sheng Chiang Combinations of tumor-associated antigens in compositions for various types of cancers
US6997074B2 (en) 2003-10-30 2006-02-14 Eaton Corporation Prediction of destination gear for progressive shift feature
US20050287068A1 (en) * 2004-06-17 2005-12-29 Bot Adrian I Efficacy of active immunotherapy by integrating diagnostic with therapeutic methods
KR20070056042A (ko) * 2004-06-17 2007-05-31 맨카인드 코포레이션 에피토프 유사체
CA2592922A1 (en) * 2004-12-29 2006-07-06 Mannkind Corporation Methods to trigger, maintain and manipulate immune responses by targeted administration of biological response modifiers into lymphoid organs
EP1838342A2 (en) * 2004-12-29 2007-10-03 Mannkind Corporation Methods to bypass cd+4 cells in the induction of an immune response
WO2006071989A2 (en) 2004-12-29 2006-07-06 Mannkind Corporation Methods to elicit, enhance and sustain immune responses against mhc class i-restricted epitopes, for prophylactic or therapeutic purposes
AU2005321898B2 (en) 2004-12-29 2012-07-19 Mannkind Corporation Use of compositions comprising various tumor-associated antigens as anti-cancer vaccines
EP1890724A2 (en) * 2005-05-13 2008-02-27 Oxxon Therapeutics Limited Compositions for inducing an immune response

Also Published As

Publication number Publication date
HK1141251A1 (en) 2010-11-05
CN101657213B (zh) 2014-02-26
WO2008100598A2 (en) 2008-08-21
CN101657213A (zh) 2010-02-24
EP2129389B1 (en) 2014-10-08
EP2481418A1 (en) 2012-08-01
WO2008100598A3 (en) 2008-12-31
AU2008216669A1 (en) 2008-08-21
US20080199485A1 (en) 2008-08-21
HK1139595A1 (en) 2010-09-24
ES2527412T3 (es) 2015-01-23
MX2009008620A (es) 2009-10-22
JP5755839B2 (ja) 2015-07-29
AU2008216669B2 (en) 2013-12-12
JP2010519205A (ja) 2010-06-03
CN103736086A (zh) 2014-04-23
EP2129389A2 (en) 2009-12-09
JP2014043459A (ja) 2014-03-13

Similar Documents

Publication Publication Date Title
AU2008216669B2 (en) A method for enhancing T cell response
Kayraklioglu et al. CpG oligonucleotides as vaccine adjuvants
Wu et al. Overview of vaccine adjuvants
Lahiri et al. Engagement of TLR signaling as adjuvant: towards smarter vaccine and beyond
Reed et al. Key roles of adjuvants in modern vaccines
Schellack et al. IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses
Akache et al. Adjuvants: engineering protective immune responses in human and veterinary vaccines
Song et al. A novel emulsion-type adjuvant containing CpG oligodeoxynucleotides enhances CD8+ T-cell-mediated anti-tumor immunity
Lampe et al. High‐and low‐molecular‐weight chitosan act as adjuvants during single‐dose influenza A virus protein vaccination through distinct mechanisms
EP2046344A2 (en) Methods to elicit, enhance and sustain immune responses against mhc class-i restricted epitopes, for prophylactic or therapeutic purposes
McCarthy et al. Review Anti-idiotype vaccines.
Ott et al. Development of vaccine adjuvants: a historical perspective
TW201217000A (en) Vaccine compositions based on sticholysin encapsulated into liposomes
WO2007122392A1 (en) Composition comprising a cytotoxic t-cell - inducing adjuvant
Storni et al. On the role of APC-activation for in vitro versus in vivo T cell priming
AU2014201422B2 (en) A method for enhancing T cell response
HK1174258A (en) A method for enhancing t cell response
HK1139595B (en) A method for enhancing t cell response
HK1141251B (en) A method for enhancing t cell response
Pavlenko et al. Priming of CD8+ T-cell responses after DNA immunization is impaired in TLR9-and MyD88-deficient mice
Linghua et al. In vivo immunostimulatory effects of CpG ODN in newborn piglets
Milligan Adjuvants: making vaccines immunogenic
AYOUB et al. Workshop S Vaccination and Immunopharmacology
Mackiewicz et al. Vaccination and immunopharmacology
Liu NanoAPC deliver antigen, IL-2 and co-stimulatory molecules to antigen specific T cells and activate viral specific T cells in chronic infections

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20130114

FZDE Discontinued

Effective date: 20171201