Neutrophil Fc gamma RI as target for immunotherapy of invasive candidiasis.

Invasive candidiasis represents a life-threatening disease for immunocompromised patients. This study focused on new immunotherapeutic approaches for systemic Candida albicans infections in a human FcgammaRI-transgenic mouse model. FcgammaRI (CD64) is a potent immunoactivating receptor on phagocytic and dendritic cells.

A single injection of polyethylene-glycol granulocyte colony-stimulating factor strongly prolongs survival of mice with systemic candidiasis.

Systemic candidiasis is a life-threatening disease occurring in immunocompromized patients. Granulocyte colony-stimulating factor (G-CSF) reduces mortality in experimental invasive candidiasis. Covalent conjugation of polyethylene-glycol (peg) to proteins increases their stability and in vivo bioactivity.

Effective phagocytosis and killing of Candida albicans via targeting FcgammaRI (CD64) or FcalphaRI (CD89) on neutrophils.

Invasive fungal infections are an increasing problem for immunocompromised patients. As an approach to improve targeting of polymorphonuclear leukocytes (PMNL) toward Candida albicans, the effect of bispecific antibodies (BsAbs) directed against C. albicans and either FcalphaRI or FcgammaRI was evaluated.

FcgammaRIa-gamma-chain complexes trigger antibody-dependent cell-mediated cytotoxicity (ADCC) in CD5+ B cell/macrophage IIA1.6 cells.

Most receptors for immunoglobulins exist as multi-subunit complexes, with unique ligand binding alpha-chains, combined with accessory signalling (gamma-, beta-, or zeta-) chains. The myeloid class I receptor for IgG (FcgammaRIa) has been shown to be dependent on the FcR gamma-chain for surface expression in vivo. In this study we assess the capacity of FcgammaRIa-gamma-chain complexes expressed in IIA1.

FcalphaRI (CD89) as a novel trigger molecule for bispecific antibody therapy.

Promising results from clinical trials with unconjugated antibodies stimulated renewed interest in immune effector mechanisms of monoclonal antibodies (MoAbs). We investigated the potential of IgA as antibody isotype for cell- or complement-mediated tumor cell lysis and assessed the potential of its myeloid Fc receptor, FcalphaRI (CD89), as trigger molecule for bispecific antibody (BsAb)-mediated immunotherapy. Comparing hapten-directed antibodies of human IgA2 with IgG1 or IgG3 isotypes, we found all three to mediate effective killing of sensitized tumor target cells in whole blood assays.