METHODS AND COMPOSITIONS FOR GENETIC THERAPY AND POTENTIATION OF ANTI-TUMOR IMMUNITY

摘要

The invention provides a preparation of tumor cell lines containing an exogenous gene encoding a polypeptide that potentiates the immune response to the tumor, for example, interleukin-2. The invention includes methods for cancer therapy by immunization with the immunopotentiating tumor cell. The invention also provides methodology whereby one can selectively ablate i n vitro and in vivo genetically altered cells. A preferred embodiment of this aspect of the invention includes a cell containing a first exogenous gene encoding an immunopatentiating polypeptide and a second exogenous gene encoding a "lethal" or "suicide" polypepticide, preferably under the control of an inducible promoter. Introduction of the second exogenous gene confers the ability to selectively kill the tumor cell by inducing a promoter in operative linkage to the gene encoding the lethal polypeptide to initiate transcription of the polypeptide. Diphtheria toxin or the thymidine kinase o f Herpes simplex virus are exemplary lethal genes. An exemplary promoter employed is tho 6-16 promoter, which is inducible with low levels of interferon. Methods for using the cells in cancer therapy are also provided: