Interleukin-4 receptor-directed cytotoxin therapy of AIDS-associated Kaposi's sarcoma tumors in xenograft- model

The elusive and enigmatic origin of AIDS-associated Kaposi's sarcoma (AIDS- KS) makes it a complex tumor and therefore difficult to treat. Here we demo nstrate that AIDS-KS cells express surface interleukin-4 (IL-4) receptors, and that IL-4 toxin (IL-4(38-37)-PE38KDEL) is specifically cytotoxic to the se cells. Intratumoral, intraperitoneal and intravenous administration of I L-4 toxin in nude mice with established subcutaneous AIDS-KS tumors caused considerable antitumor activity in a dose-dependent manner, with highest do se producing durable complete responses. Metabolic changes, including cache xia and lymphopenia, induced by KS tumors were prevented by IL-4 toxin trea tment. This report establishes IL-4(38-37)-PE38KDEL as an experimental ther apeutic agent for the treatment of AIDS-KS.