GENE-THERAPY FOR B-CELL LYMPHOMA IN A SCID MOUSE MODEL USING AN IMMUNOGLOBULIN-REGULATED DIPHTHERIA-TOXIN GENE DELIVERED BY A NOVEL ADENOVIRUS-POLYLYSINE CONJUGATE

Despite advances in conventional therapy, many lives continue to be lo st to common forms of B-cell cancers, including leukemias, lymphomas a nd multiple myeloma. We propose a novel approach to therapy of such ca ncers using controlled expression of a diphtheria toxin gene (DT-A) to kill malignant cells. We have previously demonstrated selective killi ng of various cell types, in vitro and in vivo, by cell-specific, tran scriptionally controlled expression of this gene. Organ-specific ablat ion in otherwise healthy transgenic mice has convincingly demonstrated the exquisite specificity achievable by this technique1-5. In the stu dies now described, DT-A was delivered in vitro and in vivo using a no vel gene delivery system employing DNA physically attached to the exte rior of adenovirus. After demonstrating the efficacy of gene delivery to Epstein-Barr virus transformed human B-cells in vitro, in vivo work was performed using a SCID mouse model for B-cell lymphoma, in which protection against tumor was observed. The concepts of tissue-regulate d toxin gene therapy, and this novel adenovirus gene delivery system a re discussed