CA3229447A1 - Anticorps ciblant des complexes peptidiques hla-e-hote et leurs utilisations - Google Patents

Anticorps ciblant des complexes peptidiques hla-e-hote et leurs utilisations Download PDF

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Publication number
CA3229447A1
CA3229447A1 CA3229447A CA3229447A CA3229447A1 CA 3229447 A1 CA3229447 A1 CA 3229447A1 CA 3229447 A CA3229447 A CA 3229447A CA 3229447 A CA3229447 A CA 3229447A CA 3229447 A1 CA3229447 A1 CA 3229447A1
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CA
Canada
Prior art keywords
antibody
hla
cells
domain
antibodies
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.)
Pending
Application number
CA3229447A
Other languages
English (en)
Inventor
Dapeng Li
Andrew James Mcmichael
Simon BRACKENRIDGE
Geraldine GILLESPIE
Mihai AZOITEI
Lucy C. Walters
Kevin O. Saunders
Barton F. Haynes
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.)
University of Oxford
Duke University
Original Assignee
University of Oxford
Duke University
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
Priority claimed from PCT/US2021/050537 external-priority patent/WO2022060893A1/fr
Application filed by University of Oxford, Duke University filed Critical University of Oxford
Publication of CA3229447A1 publication Critical patent/CA3229447A1/fr
Pending legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2833Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622Single chain antibody (scFv)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne des anticorps monoclonaux recombinants à maturation d'affinité (mAb) et des fragments qui se lient spécifiquement à un complexe HLA-E-peptide, y compris des complexes HLA-E-VL9, et régulent la fonction de cellule effectrice de cytotoxicité de cellules NK et/ou de lymphocytes T CD8 + positives pour l'expression en surface cellulaire de NKG2A ("NKG2A+"). Des anticorps monoclonaux ont été dérivés de manière recombinante de MAb spécifiques de HLA-E-VL9 fonctionnels isolés issus de souris transgéniques HLA-B immunisées contre un peptide HLA-E-VL9 et du répertoire des lymphocytes B humains naïfs. De tels anticorps sont peuvent réguler la cytotoxicité des cellules effectrices et peuvent de préférence reconnaître des complexes peptidiques HLA-E-VL9 exprimés sur la surface de cellules tumorales. Les anticorps monoclonaux ont été soumis à un ou à plusieurs cycles de maturation d'affinité. L'invention concerne des méthodes d'utilisation de mAb HLA-E-VL9 à maturation d'affinité pour moduler la fonction de cellules NK et/ou de lymphocytes CD8+ dans le cadre de stratégies immunothérapeutiques.
CA3229447A 2021-08-20 2022-08-19 Anticorps ciblant des complexes peptidiques hla-e-hote et leurs utilisations Pending CA3229447A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US202163235535P 2021-08-20 2021-08-20
US63/235,535 2021-08-20
PCT/US2021/050537 WO2022060893A1 (fr) 2020-09-15 2021-09-15 Anticorps ciblant des complexes peptidiques hla-e-host et leurs utilisations
USPCT/US2021/050537 2021-09-15
PCT/US2022/075241 WO2023023663A1 (fr) 2021-08-20 2022-08-19 Anticorps ciblant des complexes peptidiques hla-e-hôte et leurs utilisations

Publications (1)

Publication Number Publication Date
CA3229447A1 true CA3229447A1 (fr) 2023-02-23

Family

ID=85241120

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3229447A Pending CA3229447A1 (fr) 2021-08-20 2022-08-19 Anticorps ciblant des complexes peptidiques hla-e-hote et leurs utilisations

Country Status (3)

Country Link
EP (1) EP4388012A1 (fr)
CA (1) CA3229447A1 (fr)
WO (1) WO2023023663A1 (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9725764D0 (en) * 1997-12-04 1998-02-04 Isis Innovation HLA-E binding
EP3362475B1 (fr) * 2015-10-12 2023-08-30 Innate Pharma Agents de blocage de cd73
CN111434688A (zh) * 2019-01-11 2020-07-21 上海开拓者生物医药有限公司 Cd73抗体及其制备方法和应用

Also Published As

Publication number Publication date
EP4388012A1 (fr) 2024-06-26
WO2023023663A1 (fr) 2023-02-23

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