Composition and method for ex vivo immunomodulation and/or preservation of organs, methods and use

An immunomodulatory, ex vivo preservation technique used in the fields of pharmacy, immunology, chemistry and medicine to address issues such as limiting acute rejection and difficulty in maintaining the viability of transplanted organs

Inactive Publication Date: 2016-09-14
巴西教育和援助联盟
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0024] The present invention addresses the problems of the prior art involving difficulties in maintaining the viability of transplanted organs and in limiting acute rejection after transplantation while reducing or avoiding the use of immunosuppressants in transplant recipient patients

Method used

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  • Composition and method for ex vivo immunomodulation and/or preservation of organs, methods and use
  • Composition and method for ex vivo immunomodulation and/or preservation of organs, methods and use
  • Composition and method for ex vivo immunomodulation and/or preservation of organs, methods and use

Examples

Experimental program
Comparison scheme
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Embodiment 1

[0091] Example 1. Composition for ex vivo preservation and immunoregulation of organ cells to be transplanted. Adjust MARCH-I, Use of the substance Hsp70 of MHC II and / or CD86 in a preservation solution.

[0092] In this embodiment of the invention, the substance that modulates MARCH-I, MHC II and / or CD86 is Mycobacterium tuberculosis Hsp70 (sequence number NC_000962.2 of GenBank). This protein was achieved by subcloning the coding gene into plasmid pET23a and introducing it into Escherichia coli strain BL21. After bacterial culture and protein production, the protein was purified using an ATP-Sepharose (Sigma) column for protein purification according to Mehlert & Young. To determine protein concentration, use the fluorimetric test Quant-iT TM protein assay kit (Invitrogen) and Samples were read in a fluorometer (Invitrogen). For removal of lipopolysaccharide (LPS), the method described in Aida and Pabst using Triton X-114 (Sigma) was used. Contaminant Triton was rem...

Embodiment 2

[0192] Example 2. Screening of new molecular experiments suitable for preparing transplanted organs for ex vivo preservation and / or immunomodulatory compositions body method.

[0193] In response to the unexpected experimental results, the inventors investigated whether other molecular entities could provide the immunosuppressive effect caused by the regulation of MARCH-I, MHC II, and CD86. For this purpose, preservation compositions were initially considered to have synthetic analogues of Hsp70 (eg, some peptides) and their binding potential to MHC II was assessed in studied animals to provide the same immunosuppressant effect. The experiments conceived by the inventors provide a method of screening new molecular entities suitable for the preparation of compositions for the ex vivo preservation and immunomodulation of transplanted organs, said method comprising the following steps:

[0194] - a first step: contacting one or more molecular entities with cells having a prot...

Embodiment 3

[0222] Example 3 : Composition for preserving transplanted organs and for suppressing their rejection - increasing graft survival

[0223] Dipping treatment followed by topical treatment with Hsp70 increases skin graft survival

[0224] In order to prolong even more the graft acceptance following topical treatment with Hsp70, the inventors have implemented a novel strategy in which recipients received grafts treated with Hsp70 or OVA on day 0.

[0225] Subsequently, each animal received topical application of 2 drops of Hsp70 or OVA solution, depending on graft treatment, until day 7. That is, animals receiving grafts treated with Hsp70 received topical application of Hsp70 solution and the same topical application of OVA.

[0226] exist Figure 18 , an overview of the strategies used can be found in Item A. Notably, graft survival was much greater in Hsp70-treated animals when compared to OVA-treated animals ( Figure 18 , B and C and Table 6). Furthermore, this stra...

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Abstract

The present invention provides a composition for modulating MARCH-I, MHC II and / or CD86 in the cells of an ex vivo organ, that is to say an organ taken from a donor for subsequent transplantation in a recipient. In one embodiment, the composition comprises one or more organ preservation solutions in combination with an Hsp. In another embodiment, the composition of the invention comprises Hsp70 and / or one or more synthetic Hsp70-derived peptides. The composition of the invention provides preservation while at the same time reducing rejection of an organ, thus offering many advantages and solving various relevant technical problems: not only preserving the useful life of the organ but also initiating a process in the organ which inhibits acute rejection; lengthening the useful life of the organ in vivo; having local immunomodulating effects in the recipient; having an indirect impact on the quality of life of the transplant recipient by necessitating fewer immunossuppressive medications; inducing the activity of regulatory T cells (which are acknowledged to be immunosuppressors), reducing the expression of MHC molecules in the graft, reducing alloreactive expression in the recipient's lymph nodes, and lengthening the survival of the graft in the recipient.

Description

[0001] Related Patent Applications [0002] This patent application claims priority from Brazilian patent application BR 10 2014 002362 3 filed on January 30, 2014. technical field [0003] The present invention relates to the fields of immunology, pharmacy, chemistry and medicine. More specifically, the present invention provides compositions that modulate MARCH-I, MHC II and / or CD86 ex vivo in organ cells, ie, organ cells removed from a donor and subsequently transplanted into a recipient. In one embodiment, the composition includes one or more organ preservation solutions and Hsp. In another embodiment, the compositions of the invention comprise Hsp70 and / or one or more synthetic peptides derived from Hsp70. Compositions according to the invention reduce organ rejection while providing organ preservation, in addition to providing numerous advantages and solving a number of related technical problems: not only maintaining the lifespan of the organ, but also suppressing th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61K38/10A01N1/02
CPCA61K38/063A61K38/1774A01N1/021G01N33/505A01N1/0226A61P37/02G01N33/5088
Inventor C·B·C·博诺里诺T·D·J·博尔赫斯
Owner 巴西教育和援助联盟
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