Soluble Fc fusion proteins for biomedical research.

As a source of recombinant antigen, soluble constant fragment (Fc) fusion proteins have become valuable reagents for immunotherapy and laboratory investigations. Additional applications for these reagents include flow cytometry, immunohistochemistry, and in vitro activity assays. To aid investigators in the generation of these reagents, the materials and methods required for producing Fc fusion proteins are described.

New world clade B arenaviruses can use transferrin receptor 1 (TfR1)-dependent and -independent entry pathways, and glycoproteins from human pathogenic strains are associated with the use of TfR1.

Arenaviruses are rodent-borne viruses, with five members of the family capable of causing severe hemorrhagic fevers if transmitted to humans. To date, two distinct cellular receptors have been identified that are used by different pathogenic viruses, alpha-dystroglycan by Lassa fever virus and transferrin receptor 1 (TfR1) by certain New World clade B viruses. Our previous studies have suggested that other, as-yet-unknown receptors are involved in arenavirus entry.

Receptor use by the Whitewater Arroyo virus glycoprotein.

Whitewater Arroyo virus (WWAV) is a North American New World arenavirus, first isolated from rats in New Mexico in 1993, and tentatively associated with three human fatalities in California in 1999-2000. However, it remains unclear whether WWAV was the cause of these, or any other, human infections. One important characteristic of viruses that influences pathogenic potential is the choice of cellular receptor and the corresponding tropism of the virus.

RA8, a human anti-CD25 antibody against human Treg cells.

Although anti-CD25 antibodies exist for clinical use in patients, there is a need for the development of a human Treg antibody that will abrogate the immunosuppressive function of this small but critical T cell subtype. Based upon mounting evidence that the level of Treg cells in the tumor microenvironment correlates with clinical prognosis and stage in man, it appears that Treg cells play an important role in the tumor's ability to overcome host immune responses. In mice, the rat anti-mouse CD25 antibody PC61 causes depletion of CD25-bearing Treg cells both peripherally in lymphatic tissues and in the tumor microenvironment, without inducing symptoms of autoimmunity.

Targeted and untargeted CD137L fusion proteins for the immunotherapy of experimental solid tumors.

Introduction: CD137L is a member of the tumor necrosis factor superfamily that provides a costimulatory signal to T cells. In this study, two novel CD137L fusion proteins were produced and compared with the CD137 agonist antibody 2A.

Materials And Methods: Murine CD137L was linked to the COOH terminus of either the Fc fragment of immunoglobulin (untargeted version) or TNT-3 (targeted version), an antibody that binds to necrotic regions of tumors.

Differences in tropism and pH dependence for glycoproteins from the Clade B1 arenaviruses: implications for receptor usage and pathogenicity.

The Clade B lineage of the New World arenaviruses contains four viruses capable of causing severe hemorrhagic fevers in humans. Within this group, the B1 sub-lineage contains the pathogenic viruses Junin (JUNV) and Machupo (MACV), as well as the non-pathogenic Tacaribe virus (TCRV). In order to elucidate differences that may determine pathogenicity, we studied the entry pathways directed by the glycoproteins (GPs) from these related B1 viruses, using pseudotyped retroviral vectors and GP1 immunoadhesin constructs.

H60/TNT-3 fusion protein activates NK cells in vitro and improves immunotherapeutic outcome in murine syngeneic tumor models.

H60 is a murine minor histocompatibility antigen that binds to NKG2D and activates an effector phenotype in NK and T cells. In the present study, H60 was genetically fused to the tumor-targeting murine MAb TNT-3. The resultant fusion protein, named H60/TNT-3, was produced in NS0 cells and determined by ELISA to possess an H60 epitope.