University of Louisville Research Foundation

Georgia Tech Research Corporation

University of Missouri

Haval Shirwan

Esma S Yolcu

Kutlu G Elpek

Andres Jose Garcia

Devon Headen

Hong Zhao

Described herein are pharmaceutical compositions, medicaments and methods for providing effective immunomodulation with chimeric proteins including FasL moieties for selective and long-lasting regulation of the immune response.

Immunomodulation for the long term prevention and treatment of autoimmune diseases and foreign tissue rejection

Described herein are FasL-engineered biomaterials, as well as methods of making and using such FasL-engineered biomaterials, such as for immunomodulation, such as for inducing immunosuppression and specific immune tolerance, such as for preventing or reducing the risks of rejection of cellular or tissue grafts and/or the treatment of autoimmune disorders such as Type I diabetes. In specific embodiments, the FasL-engineered biomaterials are biotinylated microgels bound to SA-FasL.

FasL-engineered biomaterials with immunomodulatory function

Methods and compositions are provided for the persistent modification of cell membranes with exogenous proteins so as to alter the function of the cell to achieve effects similar to those of gene therapy, without the introduction of exogenous DNA. DNA sequences, the proteins and polypeptides embodying these sequences are disclosed for modulating the immune system. The modulations include down-regulation, up-regulation and apoptosis.

Alteration of cell membrane for new functions using IL-2 and streptavidin

The invention provides conjugates comprising an immune co-stimulatory polypeptide and an antigen or infectious agent. The conjugates are useful for generating or enhancing an immune response against the antigen or infectious agent. The invention also provides immune cells modified with a conjugate that are useful for generating or enhancing an immune response to an antigen or infectious agent. The invention also provides immunostimulatory moieties comprising an immune co-stimulatory polypeptide that are useful for stimulating an immune response. The invention also provides immunotherapy methods and methods of treating or preventing infections.

Immunostimulatory compositions and methods

Alteration of cell membrane for new functions

This invention provides chimeric proteins comprising an apoptosis-inducing molecule fused to a member of a binding pair that is capable of binding to a selected cell that expresses a death receptor. When the selected cell is exposed in vivo or ex vivo to the chimeric protein, the selected cell undergoes apoptosis. The preferred embodiment is FasL protein fused to streptavidin. The methods of using the chimeric proteins are especially beneficial in causing activated lymphocytes to undergo apoptosis, thus modulating the immune response. Patients with conditions such as asthma or allergy, or patients undergoing transplantation with allogeneic or xenogeneic tissue are examples of patients who benefit from the methods of this invention.

Methods of immune modulation with death receptor-induced apoptosis

Alteration of cell membrane with FasL

Fas ligand-avidin/streptavidin fusion proteins

The present invention provides methods and compositions for expanding Treg cells ex vivo or in vivo using one or more conjugates comprising a costimulatory moiety that stimulates at least one of three signals involved in Treg cell development and/or using dendritic cells pulsed with antigens and modified to display TGF-&#x3b2;, or hematopoetic stem cells or bone marrow cells modified to display TGF-&#x3b2;. The methods and compositions are useful, for example, in the treatment and prevention of autoimmune disease, including Type 1 diabetes and in preventing foreign graft rejection, as well as to establish mixed chimerism, induce tolerance to autoantigens, alloantigens or xenoantigens, beta cell regeneration, prevention of foreign graft rejection, and treatment of a genetically inherited hematopoietic disorder.

Growing community of inventors

Louisville, KY, United States of America

Haval Shirwan