Harnessing quantum dots to study, visualize, and promote immune tolerance

Patent metadata

Field	Value
Publication number	US-10898583-B2
Application number	US-201716093205-A
Country	US
Kind code	B2
Filing date	Apr 18, 2017
Priority date	Apr 18, 2016
Publication date	Jan 26, 2021
Grant date	Jan 26, 2021

Abstract

Provided are compositions and methods for promoting tolerance to auto-immune antigens. In general the compositions include quantum dots (QDs) that are in association with auto-immune peptide antigens. It is shown that QDs can be used to generate immunological tolerance by controlling the density of self-antigen on QDs. Peptide-QDs rapidly concentrate in draining lymph nodes, and co-localize with macrophages expressing scavenger receptors involved intolerance. Treatment with peptide-QDs reduces disease incidence 10-fold. The degree of tolerance and the underlying expansion of regulatory T cells correlates with the density of myelin molecules presented on QDs such that higher numbers of tolerogenic particles displaying lower levels of self-peptide are more effective for inducing tolerance than fewer particles each displaying higher densities of peptide. The disclosure is therefore relevant to promoting tolerance to antigens that are involved in a variety of autoimmune disorders.

First claim

What is claimed is:

1. A quantum dot (QD) comprising a CdSe/ZnS component, the QD having conjugated thereon a plurality of myelin peptide antigen molecules, the antigen molecules comprising HHHHHSAAAAAG (SEQ ID NO:2), wherein (H) 5 of SEQ ID NO:2 participates in Zn-coordination of the peptide antigen on the QD.

2. The QD of claim 1 , wherein the size of the quantum dot having the myelin peptide antigen molecules thereon is from 14 to 22 nm.

3. The QD of claim 1 , wherein the number of myelin peptide antigen molecules on the QD are from 15 to 65.

4. The QD of claim 1 , wherein the number of myelin peptide antigen molecules on the QD are from 13 to 59.

5. The QD of claim 1 , wherein the density of myelin peptide antigen molecules on the QD are less than or equal to 0.56 peptide antigen molecules per nm 2 of QD surface area.

6. The QD of claim 1 , wherein S in SEQ ID NO:2 acts as a flexible hinge to display the peptide away from the QD surface, and wherein (A) 5 is an alpha-helical spacer.

7. A composition comprising a plurality of quantum dots (QDs) of claim 1 .

8. The composition of claim 7 , wherein the QDs comprise a ratio of myelin peptide antigen to QD of from 1:1 to 150:1.

9. The composition of claim 8 , wherein at least 80% of the QDs in the plurality have a diameter of from 10-40 nm.

10. A method for promoting tolerance to a myelin antigen comprising administering to an individual in need thereof a composition of claim 7 .

11. The method of claim 10 , wherein subsequent to the administration regulatory T cells (T REGS ) in the individual are expanded relative to a control.

12. The method of claim 10 , wherein subsequent to the administration regulatory inflammatory T H 1 cells in the individual are not expanded relative to a control.

13. The method of claim 10 , wherein the QDs comprise a lowest density of myelin peptide antigens having 17±4 myelin peptide antigens per QD, and wherein the QDs comprise a highest density of myelin peptide antigens having 52±7 myelin peptide antigens per QD.

14. The method of claim 10 , wherein a composition comprising the plurality of QDs is administered to an individual who has a condition that comprises an autoimmune response to myelin.

15. The method of claim 14 , wherein the individual has multiple sclerosis, and wherein one or more symptoms of the MS in the individual are alleviated or inhibited from developing.

16. The method of claim 15 , wherein the QDs comprise a ratio of myelin peptide antigen to QD of less than 150:1, and wherein alleviation or inhibition of development of the MS symptoms in the individual is greater than alleviation or inhibition of symptoms of the MS relative to a control value for administration of QDs comprising a ratio of myelin peptide antigen to QD of 150:1 or higher.

17. The method of claim 15 , wherein the QDs comprise a ratio of myelin peptide antigen to QD of less than 65:1, and wherein alleviation or inhibition of development of the MS symptoms in the individual is greater than alleviation or inhibition of symptoms of the MS relative to a control value for administration of QDs comprising a ratio of myelin peptide antigen to QD of 65:1 or higher.

18. The method of claim 15 , wherein subsequent to the administration T REGS in the individual are expanded relative to a control, and/or wherein subsequent to the administration regulatory inflammatory T H 1 cells in the individual are not expanded relative to a control.

19. The method of claim 17 , wherein subsequent to the administration T REGS in the individual are expanded relative to a control, and/or wherein subsequent to the administration regulatory inflammatory T H 1 cells in the individual are not expanded relative to a control.

Assignees

• Univ Maryland
• Us Navy
• Us Gov Sec Navy

Inventors

• Jewell Christopher M
• Hess Krystina
• Medintz Igor
• Susumu Kimihiro
• Oh Eunkeu

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K49/0067

  quantum dots, fluorescent nanocrystals · CPC title

• B82Y10/00

  Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic · CPC title

• A61K47/6923

  the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb · CPC title