The United States of America, as Represented by the Secretary, Department of Health and Human Services

Other

The United States of America as Represented by the Secretary of

Children's Medical Center Corporation

Philip M Murphy

Christophe Combadiere

Joost J Oppenheim

Christopher C Broder

Derrick J Rossi

Edward A Berger

Harry L Malech

Yu Feng

Agnieszka D Czechowicz

Ji Ming Wang

Paul E Kennedy

Shao-Bo Su

Wang Hua Gong

Paejonette Jacobs

David H McDermott

Ji-Liang Gao

WangHua Gong

Yingying Le

Marie Siwicki

Ji-Ming Wang

Bao Qun Li

Thomas Rogers

Florence Guignard

H Lee Tiffany

Zhanzhuo Li

Jiliang Gao

Joy Liu

Ghalib Alkhatib

Provided are methods and compositions conditioning a patient for an allogeneic transplantation, wherein the patient's hematopoietic stem cells (HSCs) are depleted with an HSC-depleting composition and the patient is then administered allogeneic cells selected from bone marrow cells, umbilical cord blood cells, hematopoietic stem and progenitor cells (HSPCs), peripheral blood CD34cells, and peripheral blood CD34and CD90cells; optionally the patient is also administered a medicament selected from the group consisting of a T-cell depleting or inhibiting antibody or antibody fragment, NK-cell depleting or inhibiting antibody or antibody fragment, immunosuppressive drug, and any combination thereof. The HSC-depleting composition comprises a compound selected from the group consisting of: an antibody or antibody fragment with specific binding affinity to a protein displayed at the HSC surface, a conjugate comprising an HSC-recognition molecule and a toxin, and any combination thereof.

Antibody-mediated conditioning with immunosuppression to enable allogeneic transplantation

Provided herein are methods of enhancing engraftment of hematopoietic stem cells (HSC) in recipient subjects by reducing expression (or activity) of CXC chemokine receptor 4 (CXCR4). Such methods can be used in gene therapy protocols and in HSC transplantation, for example allowing this to occur without radiation or chemotherapy conditioning as is typically done in non-myeloablative HSC transplant. In some examples, gene editing methods are used to delete one copy of the CXCR4 gene before HSC or bone marrow transplantation, enhancing the efficiency and durability of donor cell repopulation.

Reducing CXCR4 expression and/or function to enhance engraftment of hematopoietic stem cells

The susceptibility of human macrophages to human immunodeficiency virus (HIV) infection depends on cell surface expression of the human CD4 molecule and CC cytokine receptor 5. CCR5 is a member of the 7-transmembrane segment superfamily of G-protein-coupled cell surface molecules. CCR5 plays an essential role in the membrane fusion step of infection by some HIV isolates. The establishment of stable, nonhuman cell lines and transgenic mammals having cells that coexpress human CD4 and CCR5 provides valuable tools for the continuing research of HIV infection. In addition, antibodies which bind to CCR5, CCR5 variants, and CCR5-binding agents, capable of blocking membrane fusion between HIV and target cells represent potential anti-HIV therapeutics for macrophage-tropic strains of HIV.

CC chemokine receptor 5 DNA, new animal models and therapeutic agents for HIV infection

The present invention relates to the discovery that T20/DP178, T21/DP107, and fragments thereof interact with members of the formyl peptide receptor family and thereby modulate cell migration and activation. Novel biological tools, prophylactics, therapeutics and methods of use of the foregoing for modulating an inflammatory response are disclosed.

T20/DP178 is an activator of human phagocyte formyl peptide receptors

The present invention relates to the discovery of molecules that inhibit viral infection and promote a host immune response to a pathogen. More specifically, the invention disclosed herein concerns molecules that interact with a FPR class receptor, inhibit HIV infection, and stimulate an inflammatory response in a subject. Embodiments of the invention include biotechnological tools, prophylactics, therapeutics, and methods of use of the foregoing, for the study, treatment, and prevention of HIV infection and the induction of an inflammatory response in a subject.

Ligands for FPR class receptors that induce a host immune response to a pathogen or inhibit HIV infection

A functional promoter for the chemokine receptor CCR5 is provided. The invention provides a nucleic acid sequence for the promoter and methods of reducing inflammation and susceptibility to HIV infection by suppressing the activity of the promoter.

Functional promoter for CCR5

This invention provides for the cloning and expression of the human Macrophage Inflammatory Protein-1.alpha. (MIP-1.alpha.)/RANTES Receptor. This receptor binds two cytokines MIP-1.alpha. and RANTES which are pro-inflammatory cytokines. The receptor is useful for assaying the levels of these cytokines in biological specimens. These cytokines play key roles in the inflammatory processes afflicting man.

Cloning and expression of the human macrophage inflammatory protein-1.alpha

An airplane parachute device includes parachutes and release mechanism mounted in the upper surface of the aircraft's fuselage. A releasable hatch, covers each parachute and release mechanism, and is in operable communication with the pilot's compartment to allow for remote controlled release. The parachutes are under similar remote control and are ejected from the parachute compartments by a coiled spring system. Each parachute is aided in opening by an inflatable collar affixed to the outer rim. A shock absorbing piston is mounted to the bottom of the parachute compartment and to the tether lines of the parachute.

Aircraft parachute safety system

Growing community of inventors

Rockville, MD, United States of America

Philip M Murphy