While conventional treatments kill cancer cells, they often kill normal cells in a non-specific fashion. In contrast, targeted drug therapy has the potential for greater specificity. Immunotoxins are one form of targeted therapy and they are agents that consist of a targeting agent (e.g. antibody molecule) linked to a toxic agent (e.g. plant or bacteria toxin). Immunotoxins are very potent and once they bind to tumor cells, the immunotoxins get inside the tumor cells and fewer than 10 molecules are lethal for the tumor cell. Unlike chemotherapy/radiotherapy which target only rapidly dividing cells (both cancerous and normal), immunotoxins are often designed to kill only cancer cells. Therefore, immunotoxins are specific for cancer cells and do not damage normal tissue. While immunotoxins have achieved some success in treating cancer patients, there are problems that have been encountered. The goal of this application is to overcome current problems by generating a new type of targeting agent. This new targeting agent, soluble T-cell receptors, will be conjugated to the plant toxin ricin and experiments will determine the efficacy of this new type of immunotoxin to target and kill cells. Soluble T-cell receptors will be cloned by PCR and expressed using the baculovirus expression system. Ricin A-chain will be linked to the T-cell receptor biochemically or genetically. This conjugate will be purified and then used to kill the murine lymphoma, BCL1, in vitro and in vivo. When successful, soluble T-cell receptors will provide a new approach for harnessing the specificity of T-cell receptors to target toxins, drugs and isotopes to tumors.
