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 demonstrate 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 these cells. Intratumoral, intraperitoneal and intravenous administration of IL-4 toxin in nude mice with established subcutaneous AIDS-KS tumors caused considerable anti-tumor activity in a dose-dependent manner, with highest dose producing durable complete responses. Metabolic changes, including cachexia and lymphopenia, induced by KS tumors were prevented by IL-4 toxin treatment. This report establishes IL-4(38-37)-PE38KDEL as an experimental therapeutic agent for the treatment of AIDS-KS.
Husain
S R
SR
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland 20892, USA.
Kreitman
R J
RJ
Pastan
I
I
Puri
R K
RK
D036002:ADP Ribose Transferases; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000818:Animals; D001427:Bacterial Toxins; D002100:Cachexia / Q000517:prevention & control; D005098:Exotoxins / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000627:therapeutic use*; D008231:Lymphopenia / Q000517:prevention & control; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000627:therapeutic use; D019948:Receptors, Interleukin-4 / Q000187:drug effects / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D015847:Interleukin-4; D010446:Peptide Fragments; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C120228:interleukin 4 (38-37)-PE38KDEL