IMMUNOTHERAPY FOR CANCER BY DIRECT GENE-TRANSFER INTO TUMORS

The goal of immunotherapy is to stimulate the immune system by modification of tumor cells or expansion of lymphocytes which respond specifically to tumor antigens. In this study, we will apply techniques of direct gene transfer to enhance the immune response against tumors in vivo. Patients with advanced cancer who have failed all effective therapy will be treated by injection of a DNA/liposome complex directly within the tumor. DNA will be used which encodes a heterodimeric cell surface protein recognized in the transplantation response. These genes include the HLA-B7 histocompatibility antigen and β-2 microglobulin gene in a non-viral eukaryotic expression vector plasmid. For this vector, a safe and effective dose to introduce this recombinant gene in HLA-B7¯ patients will be established. HLA-B7 expression will be confirmed in vivo, and the immune response stimulated by the expression of this antigen will be characterized. We will also determine whether this treatment facilitates tumor regression alone or in combination with other treatment modalities. This study will employ a similar strategy to our previous gene therapy protocol, but employs four improvements in technology, including more efficacious liposomes, optimized vector expression, catheter delivery and application to other several types of cancer. These studies will facilitate the development of other approaches, using different recombinant genes or in combination with cytokines or adoptive T cell therapy, to augment tumor immunity, and allow for greater potential efficacy. This method will also establish the safety of this non-viral approach to gene therapy, which could potentially be extended to treat a variety of other human diseases. © 1994, Mary Ann Liebert, Inc. All rights reserved.