POTENT ANTITUMOR-ACTIVITY OF A NEW CLASS OF TUMOR-SPECIFIC KILLER-CELLS

Two approaches to the antibody-directed targeting of toxic or cytolyti c activity and augmentation of cellular immune responses have been exp lored For tumour immunotherapy, but so far success has been limited(1- 3). Obstacles facing immunotherapy are the limited accessibility of an tibodies or antibody conjugates to solid tumours and the difficulty in obtaining tumour-specific cytotoxic lymphocytes(4-7). Here we generat e a new class of tumour-specific killer cells by genetically modifying lymphocytes to produce and secrete a targeted toxin against an oncopr otein overexpressed on breast and other tumour cells, The transduced l ymphocytes were shown to have potent and selective cytotoxicity to tum ours in culture and nude mouse models, The potent in vivo antitunour a ctivity is probably a result of the migration of the lymphocytes to tu mours as a targeted toxin carrier, and production and accumulation of the targeted toxins inside tumours as a producer. Our approach, which has features of both antibody-directed and cell-mediated immunotherapy , may have application in a gene therapy context.