SG11201907285XA - Methods and kits for generating mimetic innate immune cells from pluripotent stem cells - Google Patents

Methods and kits for generating mimetic innate immune cells from pluripotent stem cells

Info

Publication number
SG11201907285XA
SG11201907285XA SG11201907285XA SG11201907285XA SG11201907285XA SG 11201907285X A SG11201907285X A SG 11201907285XA SG 11201907285X A SG11201907285X A SG 11201907285XA SG 11201907285X A SG11201907285X A SG 11201907285XA SG 11201907285X A SG11201907285X A SG 11201907285XA
Authority
SG
Singapore
Prior art keywords
cells
mimetic
international
innate immune
harvest
Prior art date
Application number
SG11201907285XA
Inventor
Jieming Zeng
Shu Wang
Original Assignee
Agency Science Tech & Res
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 Agency Science Tech & Res filed Critical Agency Science Tech & Res
Publication of SG11201907285XA publication Critical patent/SG11201907285XA/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0646—Natural killers cells [NK], NKT cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4613—Natural-killer cells [NK or NK-T]
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/125—Stem cell factor [SCF], c-kit ligand [KL]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2307—Interleukin-7 (IL-7)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2315—Interleukin-15 (IL-15)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/26—Flt-3 ligand (CD135L, flk-2 ligand)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
    • C12N2502/1352—Mesenchymal stem cells
    • C12N2502/1358—Bone marrow mesenchymal stem cells (BM-MSC)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/45—Artificially induced pluripotent stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/02—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/45—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from artificially induced pluripotent stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2510/00—Genetically modified cells

Abstract

1 1-1 O GC N 1-1 00 1-1 O N C (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 16 August 2018 (16.08.2018) WIPO I PCT olimion °noI0 DIDmoIIVmoIIIII DIIIIII DID (10) International Publication Number WO 2018/147801 Al DO: Seed and culture hPSCs on OP9 cells (51) International Patent Classification: C12N 5/0783 (2010.01) A61K 35/17 (2015.01) C12N 5/10 (2006.01) A61P 35/00 (2006.01) (21) International Application Number: PCT/SG2018/050051 (22) International Filing Date: 07 February 2018 (07.02.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 10201700937P 07 February 2017 (07.02.2017) SG 10201705582S 06 July 2017 (06.07.2017) SG (71) Applicant: AGENCY FOR SCIENCE, TECHNOLO- GY AND RESEARCH [SG/SG]; 1 Fusionopolis Way #20-10 Connexis, Singapore 138632 (SG). (72) Inventors: ZENG, Jieming; c/o Institute of Bioengineer- ing and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, Singapore 138669 (SG). WANG, Shu; c/o Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, Singapore 138669 (SG). (74) Agent: YUSARN AUDREY; 24 Raffles Place #27-01 Clif- ford Centre, Singapore 048621 (SG). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(ii)) of inventorship (Rule 4.17(iv)) Published: with international search report (Art. 21(3)) with sequence listing part of description (Rule 5.2(a)) (54) Title: METHODS AND KITS FOR GENERATING MIMETIC INNATE IMMUNE CELLS FROM PLURIPOTENT STEM CELLS Figure 1 a Hematepoietic Differentiation OP9 cells e-EVLEM + 20%FBS Lyn', I, it triti Commitment OP9-tLL1 cells s-NIENI + 20 F BS + Cytokntes 1 012: Harvest LH 9: Harvest D20: Harvest D33: Harvest 040 or D47: differentiated cells differentated cells differentiated cells differentiated cells Harvest NK cells and culture on and Culture on and culture on and culture on OP9-OLL1 OP9-0LL1 OP9•01.1.1 OP9-DLL1 (57) : Human pluripotent stem cells (hPSCs), especially induced pluripotent stem cells (iPSCs) provide a promising starting material to produce mimetic innate immune cells such as natural killer (NK) cells and yS T-cells for cancer immunotherapy. To facil- itate consistent mass production, an overall manufacturing scheme to make mimetic innate immune cells from hPSCs was designed and demonstrated. Particularly, a robust protocol to differentiate hPSCs into NK cells or yS T-cells through sequential hematopoietic differentiation on stromal cell line deficient in expressing M-CSF and lymphoid commitment on stromal cell line deficient in expressing M-CSF ectopically expressing DLL1 without employing CD34+ cell enrichment and spin embryoid body formation is established. Using this two-stage protocol, the generation of functional mimetic NK cells and functional mimetic NKT-cells was demonstrated yS from hPSCs, including hESCs, peripheral blood cell-derived iPSCs (PBC-iPSCs), non-T cell-derived iPSCs or yS T cell-derived iPSCs and the use of these mimetic innate immune cells in killing cancer cells.
SG11201907285XA 2017-02-07 2018-02-07 Methods and kits for generating mimetic innate immune cells from pluripotent stem cells SG11201907285XA (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SG10201700937P 2017-02-07
SG10201705582S 2017-07-06
PCT/SG2018/050051 WO2018147801A1 (en) 2017-02-07 2018-02-07 Methods and kits for generating mimetic innate immune cells from pluripotent stem cells

Publications (1)

Publication Number Publication Date
SG11201907285XA true SG11201907285XA (en) 2019-09-27

Family

ID=63107773

Family Applications (2)

Application Number Title Priority Date Filing Date
SG11201907285XA SG11201907285XA (en) 2017-02-07 2018-02-07 Methods and kits for generating mimetic innate immune cells from pluripotent stem cells
SG10202106515SA SG10202106515SA (en) 2017-02-07 2018-02-07 Methods and kits for generating mimetic innate immune cells from pluripotent stem cells

Family Applications After (1)

Application Number Title Priority Date Filing Date
SG10202106515SA SG10202106515SA (en) 2017-02-07 2018-02-07 Methods and kits for generating mimetic innate immune cells from pluripotent stem cells

Country Status (7)

Country Link
US (1) US20190359940A1 (en)
EP (1) EP3580332A4 (en)
JP (1) JP7092281B2 (en)
CN (1) CN110691844B (en)
MY (1) MY202222A (en)
SG (2) SG11201907285XA (en)
WO (1) WO2018147801A1 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190359940A1 (en) * 2017-02-07 2019-11-28 Agency For Science, Technology And Research Methods and kits for generating mimetic innate immune cells from pluripotent stem cells
WO2019053272A1 (en) 2017-09-15 2019-03-21 King's College London Compositions and methods for enhancing gamma delta t cells in the gut
AU2019302207A1 (en) * 2018-07-13 2021-03-04 Kyoto University Method for producing γδ T cells
CN109321531A (en) * 2018-11-03 2019-02-12 上海中溢精准医疗科技有限公司 A method of gamma delta T cells induction is immunized into multipotential stem cell in peripheral blood
CN110272871B (en) * 2019-05-16 2021-08-27 安徽瑞达健康产业有限公司 Composition for stimulating and inducing expansion of mononuclear cells into gamma delta T cells and application thereof
CN111235105B (en) * 2020-03-06 2021-08-10 安徽中盛溯源生物科技有限公司 Method for differentiating human pluripotent stem cells into natural killer cells and application
CN111849913B (en) * 2020-07-31 2021-05-25 南京北恒生物科技有限公司 Engineered immune cells and uses thereof
CN112662627B (en) * 2021-01-19 2022-09-02 上海爱萨尔生物科技有限公司 Culture solution for differentiating pluripotent stem cells into natural killer cells and differentiation method
CN113440606A (en) * 2021-06-02 2021-09-28 深圳市罗湖区人民医院 Specific pluripotent stem cell tumor vaccine and preparation method and application thereof
WO2023053994A1 (en) * 2021-09-29 2023-04-06 アイ ピース， インコーポレイテッド Method for producing stem cells
CN115261318A (en) * 2021-09-29 2022-11-01 苏州艾凯利元生物科技有限公司 Method for producing natural killer cells
KR20230105166A (en) * 2022-01-03 2023-07-11 주식회사 이뮤노맥스 Method for Expansion Culture of γδ T Cell
CN116042527B (en) * 2022-09-07 2023-08-22 广州瑞臻再生医学科技有限公司 iPS cell line for promoting NK cell differentiation and construction method and application thereof

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003111595A (en) * 2001-06-25 2003-04-15 Kyogo Ito Tumor antigen
CA2519953C (en) * 2003-03-24 2016-01-05 The Scripps Research Institute Dna vaccine against tumor growth and methods of use thereof
WO2006006720A1 (en) 2004-07-13 2006-01-19 Medinet., Co.Ltd METHOD OF CULTURING ϜδT CELLS, ϜδT CELLS AND REMEDY/PREVENTIVE
JP4281071B1 (en) * 2008-07-10 2009-06-17 学校法人兵庫医科大学 Vγ9Vδ2 T cell proliferating agent, method for producing activated Vγ9Vδ2 T cells and use thereof
US8945922B2 (en) 2008-09-08 2015-02-03 Riken Generating a mature NKT cell from a reprogrammed somatic cell with a T-cell antigen receptor α-chain region rearranged to uniform Va-Ja in a NKT-cell specific way
WO2010051634A1 (en) * 2008-11-07 2010-05-14 Sunnybrook Health Sciences Centre Human progenitor t-cells
CN102459575A (en) 2009-06-05 2012-05-16 细胞动力国际有限公司 Reprogramming t cells and hematophietic cells
US8518397B2 (en) * 2009-08-14 2013-08-27 Case Western Reserve University Notch induced natural killer cell generation and therapeutic uses
US9206394B2 (en) * 2010-02-03 2015-12-08 The University Of Tokyo Method for reconstructing immune function using pluripotent stem cells
GB201013767D0 (en) * 2010-08-17 2010-09-29 Isis Innovation Identification of ligands and their use
WO2013163171A1 (en) * 2012-04-24 2013-10-31 Kaufman Dan S Method for developing natural killer cells from stem cells
JP6164746B2 (en) 2012-05-22 2017-07-19 国立大学法人 東京大学 Method for producing antigen-specific T cells
US10626372B1 (en) * 2015-01-26 2020-04-21 Fate Therapeutics, Inc. Methods and compositions for inducing hematopoietic cell differentiation
EP3310931B1 (en) * 2015-06-17 2021-11-17 The UAB Research Foundation Crispr/cas9 complex for introducing a functional polypeptide into cells of blood cell lineage
CA3003152A1 (en) * 2015-11-04 2017-05-11 Fate Therapeutics, Inc. Methods and compositions for inducing hematopoietic cell differentiation
US20180362927A1 (en) * 2015-12-08 2018-12-20 Bryce R. BKAZAR Human t cell derived from t cell-derived induced pluripotent stem cell and methods of making and using
JP7224021B2 (en) 2017-02-03 2023-02-17 国立大学法人神戸大学 Method for producing induced pluripotent stem cells
US20190359940A1 (en) * 2017-02-07 2019-11-28 Agency For Science, Technology And Research Methods and kits for generating mimetic innate immune cells from pluripotent stem cells

Also Published As

Publication number Publication date
US20190359940A1 (en) 2019-11-28
CN110691844A (en) 2020-01-14
EP3580332A4 (en) 2020-11-25
WO2018147801A1 (en) 2018-08-16
EP3580332A1 (en) 2019-12-18
JP7092281B2 (en) 2022-06-28
JP2020506713A (en) 2020-03-05
SG10202106515SA (en) 2021-07-29
MY202222A (en) 2024-04-17
CN110691844B (en) 2023-09-08

Similar Documents

Publication Publication Date Title
SG11201907285XA (en) Methods and kits for generating mimetic innate immune cells from pluripotent stem cells
SG11201407819UA (en) Improved methods of cell culture for adoptive cell therapy
SG11201811405QA (en) Improved differentiation method
SG11201900772YA (en) Gene editing of car-t cells for the treatment of t cell malignancies with chimeric antigen receptors
SG11201909331UA (en) Antigen-specific immune effector cells
SG11201804510PA (en) Biparatopic polypeptides antagonizing wnt signaling in tumor cells
SG11201803701YA (en) Methods and compositions for gene editing in hematopoietic stem cells
SG11201407175RA (en) Enhanced affinity t cell receptors and methods for making the same
SG11201807487WA (en) Generation of midbrain-specific organoids from human pluripotent stem cells
SG11201809879WA (en) Novel antibodies specifically binding to zika virus epitopes and uses thereof
SG11201908492PA (en) Truncated nkg2d chimeric receptors and uses thereof in natural killer cell immunotherapy
SG11201805186VA (en) Compositions and methods for immune cell modulation in adoptive immunotherapies
SG11201907319QA (en) Gamma delta t cells and a method of augmenting the tumoricidal activity of the same
SG11201807489PA (en) Cells expressing multiple chimeric antigen receptor (car) molecules and uses therefore
SG11201809040YA (en) Hybrid aerosol-generating element and method for manufacturing a hybrid aerosol-generating element
SG11201806002SA (en) Methods for extending the replicative capacity of somatic cells during an ex vivo cultivation process
SG11201806905UA (en) Peptides and combination of peptides for use in immunotherapy against non-small cell lung cancer and other cancers
SG11201408405WA (en) Engineered three-dimensional connective tissue constructs and methods of making the same
SG11201408297XA (en) Porous graphene oxide materials
SG11201804997XA (en) Process for preparing non-cariogenic, sustained energy release juice
SG11201904535VA (en) Prevention and treatment of bone and cartilage damage or disease
SG11201806121PA (en) Ror2 antibody compositions and related methods
SG11201809534UA (en) Methods of treating autoimmune disease using allogeneic t cells
SG11201806335RA (en) Cell culture medium
SG11201804641WA (en) Methods for generating functional hematopoietic stem cells