Immunomodulation: NK cells activated by interferon-conjugated monoclonal antibody against human osteosarcoma

A mouse monoclonal antibody raised against the human osteogenic sarcoma cell line 791T has been covalently coupled to purified human lymphoblastoid interferon alpha (IFN alpha). Conjugation does not interfere with antibody function, as the product binds to 791T cells and mediates complement-dependent tumour cell lysis to a degree equal to that of free antibody. The IFN activity, assessed by augmentation of natural killer (NK)-cell-mediated lysis, is reduced, but the conjugate does augment the killing of 791T and other tumour targets by peripheral blood NK cells. In admixture experiments the conjugate, when bound to unlabelled osteogenic sarcoma cells, also augments the killing of radiolabelled bystander cells. Neither free antibody nor the conjugate mediate antibody-dependent cellular cytotoxicity (ADCC), and augmented tumour cell lysis is a function of NK cell activation. This product provides for an alternative approach to cancer therapy via the activation of infiltrating hose effector cells using specifically targeted lymphokines.