Osiris Therapeutics, Inc.

Jdm Technologies, Inc.

Joseph D Mosca

Kevin R McIntosh

Elena N Klyushnenkova

Scott Philip Bruder

Daniel R Marshak

Kevin R Mc Intosh

Elena N Klyushenkova

This application provides a method to establish and construct cell lines expressing pathogens without destruction of the host cells. The invention allows for the formation of cell lines for the purpose of continuous expression, release, and harvesting of the pathogen and maintain the consistency of the final biological pro duct. Although the invention is intended for pathogen antigen expression, the invention allows for the production of any antigen by the described methods. The establishment of a chronically infected celline can be used for reagent, diagnostic, quantification, or vaccine purposes. We have used the procedure to select for a host cell line that naturally adapts to HIV-1 replication without affecting the host cell's ability to survive. This allowed for the establishment of a chronic HIV-1 expressing cell line that continuously expresses HIV-1 particles.

Chronic pathogen-expressing cell lines

This application provides a method to form non-infectious Biological Carrier that may be used to deliver signals to cells either in vitro or in vivo. The Biological Carriers are inactivated virus particles that have been specifically modified to give biological properties different from the virus particles deriving from an unmodified host cell that (i) expresses at least one co-stimulatory molecule and (iia) at least one antigen that can initiate an immune response, and/or (iib) express surface molecules that suppress viral replication.

Production of 'biological carriers' for induction of immune responses and inhibition of viral replication

Disclosed is a method of inducing a reduced immune response to a transplant in a recipient by treating said recipient with an amount of fibroblasts or a supernatant from a fibroblast culture effective to reduce or inhibit host rejection of the transplant. The fibroblasts or a supernatant from a fibroblast culture can be administered before, at the same time as, or after the transplant. This method is effective in reducing an immune response to a transplant without compromising the immune response to other foreign antigens. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease.

Uses of fibroblasts or supernatants from fibroblasts for the suppression of immune responses in transplantation

Disclosed is a mesenchymal stem cell and/or cell of the adipocyte lineage that (i) has been modified to have at least one exogenous antigen bound to at least one primary surface molecule of said cell such that said at least one antigen can initiate an immune response and (ii) also expresses at least one co-stimulatory molecule. The antigen is preferably a protein, polypeptide, lipid or glycolipid. The primary surface molecule is MHC I, MHC II or CD1. Also disclosed is a method for stimulating presentation of at least one exogenous antigen fragment on a mesenchymal stem cell primary surface molecule by contacting a mesenchymal stem cell that is capable of expressing at least one co-stimulatory molecule with (i) an exogenous antigen or (ii) genetic material that codes for the exogenous antigen which the mesenchymal stem cell processes into at least one antigen fragment. The method can further include contacting the mesenchymal stem cell with interferon-&#x3b3;. Also disclosed are a method for determining the state of activation of a T lymphocyte population and a method for the treatment or prevention of a disease in an animal.

Antigen presenting mesenchymal stem cells

Methods and devices using non-autologous mesenchymal stem cells comprising treating a recipient in need thereof with an effective amount of non-autologous mesenchymal stem cells, including methods and preparations for treating and regenerating connective tissue and enhancing bone marrow engraftment in an individual; and for using genetically engineered allogeneic human mesenchymal stem cells that carry within them genes of interest particularly for the expression of physiologically or pharmacologically active proteins in gene therapy for correction of genetic disorders or 'rebuilding' proteins important in tissue repair.

Uses for non-autologous mesenchymal stem cells

A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of mesenchymal stem cells effective to reduce or inhibit host rejection of the transplant. The mesenchymal stem cells can be administered before, at the same time as, or after the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with mesenchymal stem cells.

Mesenchymal stem cells for prevention and treatment of immune responses in transplantation

The present invention provides a method to modulate immune responses using antigen presenting human mesenchymal stem cells to induce specific T cell anergy. The present invention also provides a method to modulate immune responses using human mesenchymal stem cells as a platform to express molecules which will induce T cell anergy.

Mesenchymal stem cells as immunosuppressants

Methods and devices using non-autologous mesenchymal stem cells comprising treating a recipient in need thereof with an effective amount of non-autologous mesenchymal stem cells, including methods and preparations for treating and regenerating connective tissue and enhancing bone marrow engraftment in an individual; and for using genetically engineered allogeneic human mesenchymal stem cells that carry within them genes of interest particularly for the expression of physiologically or pharmacologically active proteins in gene therapy for correction of genetic disorders or &ldquo;rebuilding&rdquo; proteins important in tissue repair.

Disclosed is a method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of mesenchymal stem cells effective to reduce or inhibit host rejection of the transplant. The mesenchymal stem cells can be administered before, at the same time as, or after the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with mesenchymal stem cells.

Disclosed is a mesenchymal stem cell and/or cell of the adipocyte lineage that (i) has been modified to have at least one exogenous antigen bound to at least one primary surface molecule of said cell such that said at least one antigen can initiate an immune response and (ii) also expresses at least one co-stimulatory molecule. The antigen is preferably a protein, polypeptide, lipid or glycolipid. The primary surface molecule is MHC I, MHC II or CD1. Also disclosed is a method for stimulating presentation of at least one exogenous antigen fragment on a mesenchymal stem cell primary surface molecule by contacting a mesenchymal stem cell that is capable of expressing at least one co-stimulatory molecule with (i) an exogenous antigen or (ii) genetic material that codes for the exogenous antigen which the mesenchymal stem cell processes into it least one antigen fragment. The method can further include contacting the mesenchymal stem cell with interferon-.gamma.. Also disclosed are a method for determining the state of activation of a T lymphocyte population and a method for the treatment or prevention of a disease in an animal.

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Ellicott City, MD, United States of America

Joseph D Mosca