Tumor cells have long been known to escape normal immune recognition mechanisms. A possible therapeutic strategy that obviates the need for normal T cell recognition involves the use of bispecific antibodies. Although a number of clinical trials with bispecific antibodies have proceeded; there is much to learn about their optimization in order to take full advantage of them as drugs. The general goal of this proposal is to develop and test state of the art bispecific antibodies in an animal model for brain cancer. SV40 transgenic mice develop tumors in the brain choroid plexus, and die at a mean age of 104 +/-12 days. This animal model most resembles the human disease and thus serves as a useful preclinical test of these drugs. The specific goals of the proposed work are: 1) To examine if there is normally T cell surveilance of brain tumors in the SV40 animal model; 2) To generate monoclonal antibodies to the mouse folate receptors that are present on tumor cells from the SV4O transgenic mice; 3) To engineer, purify, and characterize bispecific antibodies to the T cell receptor and the folate receptor; and 4) To begin to test the in vivo effectiveness of the bispecific antibodies.
| Patrick, T A; Kranz, D M; van Dyke, T A et al. (1997) Folate receptors as potential therapeutic targets in choroid plexus tumors of SV40 transgenic mice. J Neurooncol 32:111-23 |
