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RU-2022109604-A - UNIVERSAL DONOR SELECTION METHOD FOR IDENTIFICATION OF NK CELL DONORS

RU2022109604ARU 2022109604 ARU2022109604 ARU 2022109604ARU-2022109604-A

Inventors

  • Ли, Дин

Assignees

  • ДЗЕ РИСЕРЧ ИНСТИТЬЮТ ЭТ НЭШНУАЙД ЧИЛДРЕН'С ХОСПИТАЛ

Dates

Publication Date
20260507
Application Date
20200914
Priority Date
20200911

Claims (20)

  1. 1. A method for selecting universal donor NK cells for therapeutic administration to a subject in need thereof, comprising: determining the KIR phenotype of candidate NK cells from an NK cell donor, wherein the KIR phenotype is indicative of the presence of one or more variably inherited inhibitory KIRs 2DL1, 2DL2, 2DL3, and 3DL1 among a population of NK cells; and selecting the candidate NK cells as universal donor NK cells for therapeutic administration, wherein the KIR phenotype is indicative of the presence of one or more variably inherited inhibitory KIRs 2DL1, 2DL2, 2DL3, and 3DL1.
  2. 2. A method for selecting NK cells from a universal donor for therapeutic administration to a subject in need thereof, comprising:
  3. obtaining the HLA genotype of candidate NK cells from an NK cell donor, wherein the HLA genotype is indicative of the presence or absence of at least two HLA alleles C1, C2 and Bw4, and thus indicative of the presence of one or more variably inherited inhibitory KIRs 2DL1, 2DL2, 2DL3 and 3DL1 among the NK cell population; and
  4. selection of candidate NK cells as universal donor NK cells for therapeutic administration, where the HLA genotype of the candidate NK cells is indicative of the presence of at least two of the HLA alleles C1, C2 and Bw4.
  5. 3. The method according to claim 1 or 2, further comprising obtaining a KIR genotype of candidate NK cells, wherein the KIR genotype is indicative of the presence or absence of at least three activating KIRs selected from the group consisting of 2DS1/2, 2DS3/5, 3DS1 and 2DS4, and wherein selecting the candidate NK cells as universal donor NK cells further comprises selecting candidate NK cells containing at least three activating KIRs 2DS1/2, 2DS3/5, 3DS1 and/or 2DS4.
  6. 4. A method for selecting universal donor NK cells for therapeutic administration to a subject in need thereof, comprising obtaining a KIR genotype of candidate NK cells, wherein the KIR genotype is indicative of the presence or absence of at least three activating KIRs selected from the group consisting of 2DS1/2, 2DS3/5, 3DS1 and 2DS4; and selecting the candidate NK cells as universal donor NK cells for therapeutic administration, wherein the KIR genotype is indicative of the presence of at least three activating KIRs 2DS1/2, 2DS3/5, 3DS1 and/or 2DS4.
  7. 5. The method according to paragraph 4, further comprising
  8. obtaining the HLA genotype of candidate NK cells, where the HLA genotype is indicative of the presence or absence of each of the HLA alleles C1, C2, and Bw4; and
  9. selection of candidate NK cells as universal donor NK cells for therapeutic administration, where the HLA genotype of the candidate NK cells is indicative of the presence of at least two of the HLA alleles from HLA C1, C2 and Bw4.
  10. 6. A method for screening a population of candidate NK cells from a donor to identify universal donor NK cells in the population to obtain a source of NK cells for therapeutic administration to subjects in need thereof, comprising obtaining the HLA genotype of the candidate NK cells from the NK cell donor, wherein the HLA genotype is indicative of the presence or absence of at least two of the HLA alleles C1, C2 and Bw4, wherein candidate NK cells containing at least two HLA alleles from HLA C1, C2 and Bw4 are identified as universal donor NK cells.
  11. 7. The method of claim 6, further comprising obtaining a KIR genotype of candidate NK cells, wherein the KIR genotype is indicative of the presence or absence of at least three activating KIRs selected from the group consisting of 2DS1/2, 2DS3/5, 3DS1 and 2DS4; wherein candidate NK cells comprising at least three activating KIRs 2DS1/2, 2DS3/5, 3DS1 and/or 2DS4 are identified as universal NK cells.
  12. 8. The method according to any one of claims 1-7, wherein the selected universal donor NK cells are histologically optimized for at least 50-85% of the recipient subjects.
  13. 9. The method of any one of claims 1-7, further comprising obtaining or having obtained seropositivity for CMV candidate NK cells, wherein selecting the candidate NK cell as a universal donor NK cell further comprises selecting the candidate NK cell that is seropositive for CMV or has high expression of NKG2C, compared to a reference level of NKG2C expression.
  14. 10. An isolated universal donor NK cell selected by the method of any one of claims 1-5, 8 or 9; or identified by screening, by the method of claim 6 or 7.
  15. 11. The isolated universal NK cell according to claim 10, wherein the NK cells are NKG2C+.
  16. 12. The isolated universal NK cell of claim 10, wherein the NK cell is activated by incubating universal donor NK cells in vitro in the presence of IL-21.
  17. 13. The isolated universal NK cell of claim 12, wherein the IL-21 used in the in vitro activation comprises at least one of soluble IL-21, IL-21 expressing feeder cells (FC21), IL-21 plasma membrane particles (PM21), and IL-21 exosomes (EX21).
  18. 14. A method for treating a malignant tumor or an infectious disease in a subject, comprising administering to the subject a donor NK cell selected by the method of any one of claims 1-5, 8 or 9; or identified by screening, by the method of any one of claims 6 or 7; or administering an isolated universal NK cell of any one of claims 10-13.
  19. 15. A method of treating a malignancy or an infectious disease in a subject, comprising (a) obtaining or having an HLA genotype-derived NK cell candidate from an NK cell donor, wherein the HLA genotype is indicative of the presence or absence of each of the HLA alleles C1, C2, and Bw4, and thus, indicative of the presence of one or more variably inherited inhibitory KIRs 2DL1, 2DL2, 2DL3, and 3DL1; (b) obtaining or having an KIR genotype-derived NK cell candidate, wherein the KIR genotype is indicative of the presence or absence of each activating KIR selected from the group consisting of 2DS1/2, 2DS3/5, 3DS1, and 2DS4; and
  20. (c) selecting a candidate NK cell as a universal donor NK cell for therapeutic administration, where (i) the HLA genotype is indicative of the presence of at least two of the HLA alleles from HLA C1, C2 and Bw4; and (ii) the KIR genotype is indicative of the presence of at least three activating KIRs 2DS1/2, 2DS3/5, 3DS1 and/or 2DS4.