Application of NK (Natural Killer) cells, NK cell reinfusion preparation and combined preparation

A technology of NK cells and preparations, applied in the field of biomedicine, can solve the problems of limited prevention and treatment effect of antiviral drugs, cytomegalovirus infection, virus-resistant strains, etc., to promote HCMV clearance, NK cell phenotype maturation, prevention Effects of HCMV infection

Active Publication Date: 2022-08-02
PEOPLES HOSPITAL PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the number and function of immune cells have not been restored to normal levels in the early stage after transplantation, cytomegalovirus infection is very prone to occur, which increases the risk of transplant-related death and leads to poor transplant outcomes
The preventive and therapeutic effects of antiviral drugs are limited, and long-term application of antiviral drugs will lead to the emergence of drug-resistant strains of the virus, and can cause a series of drug side effects such as obvious bone marrow suppression and renal function damage

Method used

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  • Application of NK (Natural Killer) cells, NK cell reinfusion preparation and combined preparation
  • Application of NK (Natural Killer) cells, NK cell reinfusion preparation and combined preparation
  • Application of NK (Natural Killer) cells, NK cell reinfusion preparation and combined preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1 Mouse model experiment:

[0061] After 6-8 weeks of female NSG mice were irradiated with a sublethal dose of X-ray, HCMV-IGG seropositive G-CSF-mobilized peripheral blood stem cells were reinfused through the tail vein 1×106 / mouse; 2 weeks later , MRC-5 cells infected with HCMV virus strain AD169 were injected intraperitoneally; 4 weeks after transplantation, 1 × 10 NK cells or primary NK cells were adoptively reinfused. 7 50,000 units of IL-2 were injected intraperitoneally every other day after the NK cells were reinfused. The liver, spleen and lung of mice were harvested on the 14th day after NK cell reinfusion, and flow cytometry was used to detect the proportion of NK cells; based on in situ hybridization, HCMV-RNA probe was used to detect the number of HCMV-positive cells.

[0062] figure 1 The proportion of NK cells in the liver, spleen, lung, and periphery after 14 days of NK cell infusion is shown.

[0063] Depend on figure 1 It can be seen that a...

Embodiment 2

[0066] Example 2 Clinical study:

[0067] 10 days before the donor's haplotype hematopoietic stem cell transplantation, collect 60-80 ml of peripheral blood from the donor (determined by the WBC count in the donor's peripheral blood), or collect peripheral blood stem cells (3-4 ml) after the donor's mobilization, and separate PBMCs Cryopreservation, those who meet the inclusion criteria, the donor PBMC2*10 will be resuscitated 10 days after transplantation 7 , to initiate donor-derived NK culture.

[0068]20 patients who underwent haplotype hematopoietic stem cell transplantation were selected to be included as NK reinfusion objects. Enrollment conditions: (1) Diagnosed as: acute leukemia, or MDS, MM or lymphoma. (2) Aged 16-65 years old; (3) Donor seropositive for HCMV-IGG; (4) Negative for HCMV within 20 days after transplantation; (5) No grade 1-4 aGVHD occurred within 20 days after transplantation, or aGVHD has been resolved and The dose of glucocorticoid < 0.5 mg / kg / d w...

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Abstract

According to the application of the NK cells, the NK cell reinfusion preparation and the combined preparation, NK cell reinfusion can prevent cytomegalovirus infection, eliminate cytomegalovirus infection and promote immune reestablishment of the NK cells, the NK cell reinfusion is safe and good in tolerance, serious side effects related to infusion do not occur, and in addition, the NK cell reinfusion preparation can be used for preventing cytomegalovirus infection, eliminating cytomegalovirus infection and promoting immune reestablishment of the NK cells. By adopting the NK cell reinfusion, the occurrence of virus drug-resistant strains is not caused, a series of drug side effects such as obvious myelosuppression and renal function impairment are also not caused, and the phenotype of the reconstructed NK cell in the body of a patient after the NK cell reinfusion is more mature and the function is stronger.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to the application of NK cells, NK cell reinfusion preparations and combined preparations. Background technique [0002] After hematopoietic stem cell transplantation or solid tumor transplantation, the most common complication is cytomegalovirus (CMV) infection, accounting for nearly 50% of transplant-related deaths. Since the number and function of immune cells have not been rebuilt to normal levels in the early post-transplantation period, CMV infection is highly prone to occur, which increases the risk of transplantation-related death and leads to poor transplantation outcomes. The preventive and therapeutic effects of antiviral drugs are limited, and long-term use of antiviral drugs can lead to the emergence of virus-resistant strains, and can cause a series of drug side effects such as obvious bone marrow suppression and renal function damage. Therefore, the prevention and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/17A61K38/20A61P31/22
CPCA61K35/17A61K38/2013A61P31/22A61K2300/00Y02A50/30
Inventor 黄晓军赵翔宇商倩楠余星星
Owner PEOPLES HOSPITAL PEKING UNIV
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