Cytotoxic T cells play an important role in recovery from viral infections. Infusion of virus specific T cells has been shown to be effective in speeding recovery from infection. Unfortunately, it is difficult to utilize this finding in humans because of the need for major histocompatibility complex restriction. In past publications, we have shown that antibodies which have the ability to bind to two different antigens simultaneously can activate T cells to kill virus infected cells. These antibodies, termed bifunctional antibodies, bind and trigger killer T cells with one arm and virus antigen expressed on the surface of infected cells with the other. In this way, they redirect the lytic payload of CTL against virus infected targets. In this project, we are attempting to determine the effectiveness of this approach in speeding recovery or reducing the severity of influenza virus infection in mice. We also plan to utilize this approach to combat vesticular stomatis virus and a recombinant influenza virus which contains the V3 loop of the HIV virus. We have demonstrated the efficacy of this technique in vitro and would now like to perform in vivo experiments. The T cells which we will use for immunotherapy are produced following short culture with staphylococcal enterotoxin B (SEB). T cells activated in this way may represent a potent source of activated T cells for immunotherapy. In addition, we will test antibody SEB conjugates to determine if they can be used to target T cells against virus in infected cells in vitro and in vivo.
| Isobe, H; Moran, T; Li, S et al. (1995) Presentation by a major histocompatibility complex class I molecule of nucleoprotein peptide expressed in two different genes of an influenza virus transfectant. J Exp Med 181:203-13 |
| Moran, T M; Toy, E; Kuzu, Y et al. (1995) Staphylococcal enterotoxin B-activated T cells can be redirected to inhibit multicycle virus replication. J Immunol 155:759-65 |
| Pricop, L; Brumeanu, T; Elahi, E et al. (1994) Antibody response elicited by T-dependent and T-independent antigens in gene targeted kappa-deficient mice. Int Immunol 6:1839-47 |
