Antigen-presenting cells for neuroprotection and nerve regeneration

A technology of antigens and cells, applied in the direction of nervous system antigen components, extracellular fluid diseases, nervous system diseases, etc., can solve the problems that the exact pathway has not been fully elucidated

Inactive Publication Date: 2005-12-07
YEDA RES & DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] Dendritic cells (DCs) are derived from hematopoietic stem cells of the myeloid lineage, but the exact pathway by which they occur has not been fully elucidated

Method used

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  • Antigen-presenting cells for neuroprotection and nerve regeneration
  • Antigen-presenting cells for neuroprotection and nerve regeneration
  • Antigen-presenting cells for neuroprotection and nerve regeneration

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0132] Example 1: Identification of bone marrow-derived DC's

[0133] First, we identified the purity of DC products and the maturity of cells. The expression of co-stimulatory B7.2 (CD86) and MHC-II molecules on the surface of bone marrow-derived DC can be analyzed by flow cytometry. Such as Figure 1A As shown, when cells were harvested for injection (day 7), the majority of cells (94%) expressed B7.2 and MHC-II, whereas at the day of culture initiation (day 0), these DC markers were only 1.6 % of cells expressed.

[0134] Other types of cells that express high levels of B7.2 and MHC-II include macrophages and B cells. Therefore, we analyzed the cultures by flow cytometry on day seven for the expression of the macrophage marker ED-1 and the B cell marker CD45RA. Figure 1B The histogram of shows that the cells are negative for both markers.

[0135] We also examined the extent of DC maturation and whether it was affected by exposure to antigen. Before and after the cel...

Embodiment 2

[0136] Example 2: Effects of dendritic cells pulsed with MBP 87-99 or its analog MBP-A91 on rats suffering from SCI: Local implantation of bone marrow-derived DCs exposed to myelin peptides promotes functional recovery of SCI

[0137] Severe contusion injury was performed on male SPD rats according to the method described in section (e). Immediately after injury, bone marrow-derived DCs pulsed (by culturing for 2 h) by local injection of MBP peptide 87-99 or the modified (no longer encephalitogenic) peptide MBP-A91 were used in rats as described in Methods for treatment. The control group was locally injected with vehicle (PBS). Functional recovery was assessed by the BBB Motor Scale on a scale of 0-21 (Basso et al., 1996), where 0 indicates immobility and 21 indicates intact mobility. Rats' identities were masked to ensure blinded scoring.

[0138] After severe contusion and local injection of PBS, rats showed very limited recovery from initial shock (Figure 2). However, wi...

Embodiment 3

[0142] Example 3: Perspective on the Immunological Mechanism of Spinal Cord Injury Repair Caused by DC

[0143] To determine whether the observed neuroprotective effects of DC treatment were T cell-dependent, we injected MBP-A91-pulsed DC locally into spinal cord-damaged male SPD rats that had been thymectomized at birth and thus lacked mature T cells middle. In the absence of normal T cell function, DCs pulsed with MBP-A91 had no significant effect on functional recovery ( Figure 6 ). Results shown are from one representative experiment out of three with thymectomized SPD rats; similar results were obtained in both males and females. It must be noted that due to differences in animal weights between experiments, we generally compare BBB scores between groups within the same experiment. Therefore, the relatively higher BBB scores in the control group of thymectomized animals should not be taken as evidence that DCs fail to promote repair in these animals. The absence of T...

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Abstract

Pharmaceutical compositions and methods for preventing or inhibiting neuronal degeneration, or for promoting nerve regeneration, in the central nervous system (CNS) or peripheral nervous system (PNS), in the treatment of an injury, disorder or disease of the CNS or PNS, comprise antigen-presenting cells, preferably dendritic cells, that have been pulsed with an agent selected from the group consisting of: (a) a nervous system (NS)-specific antigen or an analog thereof; (b) a peptide derived from an NS-specific antigen or from an analog thereof, or an analog or derivative of said peptide; (c) a copolymer selected from the group consisting of Copolymer 1, a Copolymer 1-related peptide or polypeptide, and poly-Glu<50> Tyr<50>; and (d) a non-self antigen.

Description

field of invention [0001] The present invention relates to compositions and methods, and in particular, to compositions comprising antigen-presenting cells, preferably dendritic cells, pulsed with a suitable antigen and the role of said antigen-pulsed cells in preventing or inhibiting central nervous system (CNS) or Use in methods of degeneration of peripheral nervous system (PNS) neurons or promotion of neurogenesis. [0002] Abbreviations: APC: antigen-presenting cell; APL: modified peptide ligand; CNS: central nervous system; BBB: BBB open-field locomotion scale (Basso, Beattie and Bresnahan open-field locomotion scale); DC: dendritic cell; EAE: Experimental autoimmune encephalomyelitis; GM-CSF: granulocyte-macrophage colony-stimulating factor; MBP: myelin basic protein; MHC: major histocompatibility complex; NS: nervous system; PNS: peripheral nervous system ; RT-PCR: reverse transcription-polymerase chain reaction; SCI: spinal cord injury. Background of the invention ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00C12N5/07C12N5/0784C12N5/0793
CPCA61K39/0007A61K2039/5154A61P17/02A61P21/02A61P25/00A61P25/02A61P25/08A61P25/14A61P25/16A61P25/18A61P25/22A61P25/28A61P25/36A61P27/02A61P27/06A61P3/02A61P43/00A61P7/04A61P9/10
Inventor M·埃森巴奇-施瓦茨A·科亨
Owner YEDA RES & DEV CO LTD
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