There have been initial reports of success in treating human tumors, primarily lymphomas, with monoclonal antibodies. Unfortunately, previous experience suggests that antibodies, even of high affinity and specificity, are quite limited in their ability to destroy large tumor cell populations. It is for this reason that so much is heard of adding toxins or chemotherapeutic agents to monoclonal antibodies to increase their cytotoxic capacities. The immune system does, however, have an alternative means much more able to deal with unwanted cell burdens. This is the cellular immune mechanism which has been manipulated with increasing success in animal model tumors and has been shown under experimental conditions to be able to deal with the elimination of sizeable tumors. In the last decade, we have learned a great deal about cellular immunity to tumors. The nonspecific activity of natural killer cells remains to be harnessed. Still more attractive is the specific cytotoxicity of T cells which can be sensitized in vitro as well as in vivo. The availability of T cell growth factor (IL2) now makes it possible to grow sensitized T cells in culture and clone them to assure defined specificity. It is important this capacity be further developed for human tumors so that cloned T cell lines with stable specificity will become available for human trials. This application is directed to developing T cell clones cytotoxic for human sarcomas. The proposed Principal Investigators have experience in the isolation and characterization of human T cell clones and an established record of productivity in the study of human sarcoma antigens, including the production of monoclonal antibodies to sarcoma markers.
| Slovin, S F; Maguire Jr, H C; Mastrangelo, M J (1990) The role of autologous tumor cells in preventing lymphokine-activated killer cell induction in vitro. Cancer 66:2541-6 |
| Slovin, S F; Lackman, R D; Mastrangelo, M J (1987) HLA-A2 in sarcomas: an immunobiologic perspective. Transplantation 43:923-5 |
| Slovin, S F; Lackman, R D; Ferrone, S et al. (1986) Cellular immune response to human sarcomas: cytotoxic T cell clones reactive with autologous sarcomas. I. Development, phenotype, and specificity. J Immunol 137:3042-8 |
| Hirshaut, Y; Slovin, S F (1985) Harnessing T-lymphocytes for human cancer immunotherapy. Cancer 56:1366-73 |
