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

摘要

2091346 9205262 PCTABS00011 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 in 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 immunopotentiating polypeptide and a second exogenous gene encoding a "lethal" or "suicide" polypeptide, 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 of Herpes simplex virus are exemplary lethal genes. An exemplary promoter employed is the 6-16 promoter, which is inducible with low levels of interferon. Methods for using the cells in cancer therapy are also provided.