RESUMEN
The requirement of high doses of interferon (IFN) during therapy severely restrict its application. Thus a model using an Epstein-Barr virus (EBV) membrane antigen (MA) specific monoclonal antibody (MAb) was developed to assess the feasibility of coupling minimal amounts of IFN to a MAb and specifically delivering the IFN to the target cells. Coupled IFN was first shown to retain fully both its anti-viral and anti-proliferative properties when tested on human tumor cell lines QIMR-WIL (EBV-MA+) and the U-266 (EBV-MA-). A series of in vitro pulsing experiments demonstrated the specific targeting of both the anti-viral and anti-proliferative properties of IFN to the EBV-MA+ QIMR-WIL cells and not EBV-MA- cell lines.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Herpesvirus Humano 4/inmunología , Interferón Tipo I/administración & dosificación , Antígenos Virales/inmunología , Carcinoma de Células Escamosas , División Celular/efectos de los fármacos , Línea Celular , Transformación Celular Viral , Herpesvirus Humano 4/efectos de los fármacos , Humanos , Interferón Tipo I/farmacología , Neoplasias Laríngeas , Mengovirus/efectos de los fármacosRESUMEN
We present in vitro experiments demonstrating the feasibility of specifically targeting IFNs by coupling to monoclonal antibodies (MAbs). Human interferon alpha (HuIFN-alpha), both natural and recombinant, were coupled to Epstein-Barr virus (EBV) membrane antigen (MA) specific MAbs and shown to retain full antiviral and antiproliferative activities when tested on several human cell lines. A series of in vitro pulsing experiments demonstrated that a minimum amount of MAb-delivered IFN exerts pronounced antiviral and antiproliferative effects on human QIMR-WIL target cells which carry EBV (viral) membrane antigens (EBV-MA+) and not on U-266 or Hep2 cell lines (EBV-MA-). Additionally the antiproliferative action of MAb-coupled rIFN-alpha appeared to be enhanced compared with that of uncoupled.