| 摘要 |
The use of classical superantigens for treatment of cancer has resulted in a low response rates and serious toxicity in humans which is attributable, in part, to the presence of preformed superantigen specific antibodies in the plasma of treated patients. The present invention addresses this problem by providing a method for treating tumors comprising the administration of one or a plurality of egc (enterotoxin gene cluster) staphylococcal enterotoxins comprising staphylococcal enterotoxins G, I, M, N, O. These superantigens in native unmodified form can be administered intrathecally, intratumorally, intravenously to humans with advanced lung cancer while resolving pleural effusions and prolonging survival to 300% above control patients treated with talc pleurodesis. Intratumoral egc superantigens induces a significant and sustained reduction of the tumor size. In contrast to classic Sags, the egc superantigens induced minimal toxicity, are rarely associated with the presence of preformed antibodies and are used as a plurality with a broad T cell Vbeta profile. Useful egc superantigen compositions for parenteral administration native egc enterotoxins, homologues, fragments and fusion proteins of native egc enterotoxins capable of activating a broad spectrum of T cells expressing T cell receptor/alpha motifs. T cell survival-enhancing cytokines IL-7, Il-15, Il-23 are used. together with parenteral egc SE therapy. Also disclosed is combined therapy that includes parenteral, intratumoral or intrathecal superantigen compositions in combination with (i) intratumoral low, non-toxic doses of one or more chemotherapeutic drugs or (ii) systemic chemotherapy at reduced and non-toxic doses of chemotherapeutic drugs or (iii) radiation therapy or (iv) anti-angiogenic and tyrosine kinase inhibitors. |
