Canadian Blood Services

Canadian Bllood Services

Canadian Blood Cervices

Mark D Scott

Duncheng Wang

Wendy M Toyofuku

Elisabeth Maurer

Jayachandran N Kizhakkedathu

Sandra M Ramirez-Arcos

Nobu Kitamura

Ducheng Wang

This invention relates to acellular-based therapies for decreasing the level of regulatory T cells (Treg) and/or increasing the level of pro-inflammatory T cells (Th17) to favor immune stimulation. To provide these therapeutic effects, an allogeneic leukocyte population is contacted with another leukocyte population and the acellular components produced are isolated. The leukocyte populations are contacted so as to allow pro-inflammatory allo-recognition. Acellular-based preparations and processes for achieving therapy are also provided.

Acellular pro-inflammatory compositions, process for making same and methods of using same

This disclosure relates to a cellular-based therapies for modulating the level of regulatory T cells (Treg) and/or the level of pro-inflammatory T cells (Th17/Th1). To provide these therapeutic effects, a combination comprising at least one a cellular pro-tolerogenic preparation and at least one a cellular pro-inflammatory preparation are administered sequentially.

Combination therapy of acellular pro-tolerogenic and pro-inflammatory preparations for modulating the immune system

This invention relates to cellular-based therapies for increasing the level of regulatory T cells (Treg) and/or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. To provide these therapeutic effects, a non-proliferative allogeneic leukocyte population is contacted with another leukocyte population. The non-proliferative allogeneic leukocyte population is modified to bear on its surface a low-immunogenic biocompatible polymer so as to prevent pro-inflammatory allo-recognition with the latter leukocyte population. Cellular-based preparations and processes for achieving cellular therapy are also provided.

Method for inducing immune tolerance using non-proliferative polymer-modified allogeneic leukocytes

This invention relates to pro-tolerogenic preparations capable of increasing the level of regulatory T cells (Treg) and/or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. The pro-tolerogenic preparation is enriched in at least one species of miRNAs and is obtained by contacting two allogeneic leukocyte populations wherein at least one of the two populations is modified with a low-immunogenic biocompatible polymer. Acellular pro-tolerogenic compositions, process for making such composition as well as therapeutic uses of such compositions are also provided.

Acellular pro-tolerogenic compositions and process for making same

This invention relates to pro-tolerogenic preparations capable of increasing the level of regulatory T cells (Treg) and/or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. The pro-tolerogenic preparation is enriched in at least one species of miRNAs and is obtained by contacting two allogeneic leukocyte populations wherein at least one of the two populations is modified with a low-immunogenic biocompatible polymer. Therapeutic uses intended for the treatment/prevention of auto-immune diseases of such compositions are also provided.

Acellular pro-tolerogenic compositions for the treatment/prevention of auto-immune diseases

This invention relates to pro-tolerogenic preparations capable of increasing the level of regulatory T cells (Treg) and/or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. The pro-tolerogenic preparation is enriched in at least one species of miRNAs and is obtained by contacting two allogeneic leukocyte populations wherein at least one of the two populations is modified with a low-immunogenic biocompatible polymer. Therapeutic uses for preventing or limiting graft rejection and GVHD of such compositions are also provided.

Acellular pro-tolerogenic compositions for treatment/prevention of graft rejection

This invention relates to cellular-based therapies for increasing the level of regulatory T cells (Treg) and/or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. To provide these therapeutic effects, two allogeneic leukocyte populations are contacted (in vivo, in vitro or ex vivo) and one of these leukocyte population is modified to bear on its surface a low-immunogenic biocompatible polymer so as to prevent pro-inflammatory allo-recognition. Cellular-based preparations and processes for achieving cellular therapy are also provided.

Method for inducing immune tolerance using viable polymer-modified allogeneic leukocytes

A chelation structure and method of forming and using the chelation structure. The chelation structure has a backbone that includes a linear sequence of monomeric backbone units, at least one polymer side chain, and at least one chelator side chain. The side chains are each covalently coupled to the backbone at one of the monomeric backbone units by a bond that is independently biodegradable or non-biodegradable. The chelation structure is synthesized by Radical Addition Fragmentation Transfer (RAFT), Atom Transfer Radical Polymerization (ATRP), or Free Radical Polymerization (FRP). The chelation structure, individually or in combination with a shuttle chelator, may be introduced into a mammal to bind an amount of a substance in a mammal, the substance being at least one of a metal and heme. The chelation structure has a log stability constant exceeding that of the shuttle chelator for binding the substance within cells of the mammal.

High molecular weight chelation structure

A method for storing and using platelets and an associated platelet structure. At least one modified platelet is formed. Each modified platelet includes a platelet and at least one polymerated chemical. Each polymerated chemical includes a polymer covalently bonded directly to the platelet or includes the polymer and a linker molecule such that the linker molecule is covalently bonded to the platelet and the polymer is covalently attached to the linker molecule. The polymer of each polymerated chemical of each modified platelet is polyethylene glycol (PEG) or a PEG derivative. Forming each modified platelet does not include modifying the platelet membrane of each platelet with a glycan-modifying agent. The at least one modified platelet is stored in a temperature range below 0&#xb0; C. After being stored, the at least one modified platelet may be introduced into a subject to treat a condition related to a reduced platelet function.

Cold storage of pegylated platelets at about or below 0&#xb0; C.

A method for preventing bacterial biofilm formation in a blood product, the method comprising modifying a blood product with a polymer selected from the group consisting of polyethylene glycol (PEG), PEG derivatives and mixtures thereof. Preventing bacterial biofilm formation in this way increases the planktonic to adherent ratio of any contaminating bacteria, and thereby facilitates detection of bacterial contamination.

Method for enhancing the detection of contamination in a cellular blood product by covalently binding a hydrophilic polymer to the cell membrane

A method for storing and using platelets and an associated platelet structure. At least one modified platelet is formed. Each modified platelet includes a platelet and at least one polymerated chemical. Each polymerated chemical includes a polymer covalently bonded directly to the platelet or includes the polymer and a linker molecule such that the linker molecule is covalently bonded to the platelet and the polymer is covalently attached to the linker molecule. The polymer of each polymerated chemical of each modified platelet is polyethylene glycol (PEG) or a PEG derivative. Forming each modified platelet does not include modifying the platelet membrane of each platelet with a glycan-modifying agent. The at least one modified platelet is stored in a temperature range below 20&#xb0; C. for at least one hour. After being stored, the at least one modified platelet may be introduced into a mammal.

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Surrey, Canada

Mark D Scott