Autoantigenic peptides (calvicifiv), presented by tolerogenic dentritic cells, useful for the personalized treatment of rheumatoid arthritis

Patent metadata

Field	Value
Publication number	US-2023086469-A1
Application number	US-201917638770-A
Country	US
Kind code	A1
Filing date	Aug 30, 2019
Priority date	Aug 30, 2019
Publication date	Mar 23, 2023
Grant date	—

Abstract

The present invention provides an immunomodulatory composition useful for treating or preventing joint damage comprising at least a set of peptides possessing an amino acid sequence having at least 80%, 85% and 90% sequence identity with the peptides corresponding to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4 and a method for the treatment or prevention of joint damage comprising the steps of a) extract monocytes from a patient with a rheumatological disease; b) culture the monocytes extracted in the previous step in AIM-V medium with GM-CSF and IL-4; c) wash the monocytes and add dexamethasone; d) load the tDCs with the immunomodulatory composition comprising autoantigenic peptides; e) add MPLA; and f) incorporate the tDCs loaded with autoantigenic peptides into the patient. The present invention includes methods for the treatment or prevention of rheumatological disease comprising a wide range of tDCs performed by different protocols.

First claim

1 . An immunomodulatory composition comprising one or more peptides having an amino acid sequence of at least 90% or 95% sequence identity to an amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, or SEQ ID NO:6.

2 - 4 . (canceled)

5 . An immunomodulatory composition comprising antigen-presenting cells, wherein the antigen-presenting cells are loaded with one or more peptides as defined in claim 1 .

6 . The immunomodulatory composition according to claim 5 , wherein the antigen-presenting cells are tolerogenic dendritic cells.

7 . The immunomodulatory composition according to claim 5 , further comprising a pharmaceutically acceptable excipient selected from a group consisting of diluents, coadjuvants, buffering agents, surfactants, cosolvents and preservatives.

8 . The immunomodulatory composition according to claim 7 , wherein the pharmaceutically acceptable excipient is selected from a group consisting of sterile saline solution, phosphate buffered saline (PBS) solution, and Ringer-lactate solution.

9 . The immunomodulatory composition according to claim 5 , further comprising an additional active pharmaceutical ingredient.

10 . The immunomodulatory composition according to claim 9 , wherein the additional active pharmaceutical ingredient selected from the group consisting of disease modifying anti-rheumatic drugs (DMARDs) including methotrexate, azathioprine, bucillamine, chloroquine, cyclosporin, doxycycline, hydroxychloroquine, intramuscular gold, leflunomide, levofloxacin and sulfasalazine; folinic acid, D-pencillamine, gold auranofin, gold aurothioglucose, gold thiomalate, cyclophosphamide and chlorambucil; tumor necrosis factor (TNF)-alpha inhibitors including infliximab, adalimumab, etanercept and golimumab; interleukin-1 inhibitors including anakinra; T-cell modulators including abatacept; B-cell modulators including rituximab; and interleukin-6 inhibitors including tocilizumab.

11 . (canceled)

12 . (canceled)

13 . A method for treatment or prevention of a rheumatological disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an immunomodulatory composition as defined in claim 1 .

14 . The method according to claim 13 , wherein the rheumatological disease is Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA) or Juvenile Rheumatoid Arthritis (JRA).

15 . A method for treatment or prevention of joint damage comprising following steps:
(i) extracting monocytes from a patient with Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA), Juvenile Rheumatoid Arthritis (JRA) or another related disease; (ii) culturing the monocytes extracted in step (i), washing and differentiating to tolerogenic dendritic cells (tDCs); (iii) loading the tDCs with the immunomodulatory composition of claim 1 for obtaining loaded tDCs; and (iv) administering the loaded tDCs of step (iii) to the patient.

16 . The method according to claim 15 ,
wherein a serum-free media in the presence of 100 to 1000 U/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 100 to 1000 U/ml of interleukin-4 (IL-4) is used for culturing monocytes extracted.

17 . (canceled)

18 . The method according to claim 15 , wherein the loaded tDCs are administered to the patient via subcutaneous injection, intravenous injection, or intraarticular injection.

19 . (canceled)

20 . (canceled)

21 . The method according to claim 15 , wherein the tDCs administered to the patient have a low level of co-stimulatory molecules.

22 . The immunomodulatory composition according to claim 8 , wherein said composition further comprises serum or autologous serum.

23 . The method according to claim 15 , wherein the step (iii) further comprises adding 1 to 50 μg/ml of monophosphoryl lipid A (MPLA) to the loaded tDCs.

Assignees

• Univ Chile

Inventors

• Aguillón Gutiérrez Juan Carlos
• Catalán Martina Diego Francisco
• Soto Saez Lilian Andrea
• Maggi Orellana Jaxaira Amilene
• Aravena Madariaga Octavio Alexis
• Schinnerling Katina

Classifications

• A61K2039/577

  tolerising response · CPC title

• A61K40/416

  Antigens related to auto-immune diseases; Preparations to induce self-tolerance · CPC title

• A61K40/24

  Antigen-presenting cells [APC] · CPC title

• A61K40/22

  Immunosuppressive or immunotolerising · CPC title

• A61K40/19

  Dendritic cells · CPC title