T-cell malignancies account for 15% of all lymphomas and current treatments do not usually yield significant long-term remission. The applicants propose to treat T-cell lymphoma by inducing a specific cellular immune response to """"""""reject"""""""" only the certain proliferating T-cells. The Holy Grail of cancer immunotherapy is the identification of specific tumor markers that can be used to teach the immune system to remove the undesired population of cells while leaving other cells intact. They believe that a T-cell receptor should act as a tumor marker for a particular T-cell lymphoma. If sufficient quantities of soluble T-cell receptor were available then treatment of lymphoma by vaccination might be feasible. However, T-cell receptors are not naturally expressed in soluble form. The applicants propose to solve this problem by producing recombinant soluble T-cell receptor chains in insect cells. In Phase I they will test the feasibility of this therapeutic approach in an animal model. They will pulse autologous professional antigen presenting cells with recombinant mouse T-cell receptor beta chain ex vivo ant transfer the treated cells into mice prior to challenge with a tumorigenic T-cell line. If successful, they will extend their studies to human T-cell receptors in Phase II and clinical trials in Phase III.
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