title: New Life for Immunotoxin Cancer Therapy.
abstract: Immunotoxins are targeted anticancer therapeutics that kill cancer cells using a cytotoxic bacterial toxin payload. Their development for use in solid tumor malignancies was delayed due to issues with their immunogenicity and limited therapeutic window. However, new research has rejuvenated the field. Coadministration with a lymphocyte-depleting regimen of pentostatin and cyclophosphamide can delay antidrug antibody formation, increasing the number of treatment cycles that patients can receive and resulting in durable responses in heavily pretreated patients. In addition, a new generation of immunotoxin molecules with reduced immunogenicity and nonspecific toxicity has been developed through protein engineering techniques, and one has recently entered the clinic. In preclinical studies in mouse models, these new agents are effective against many tumor types as single agents, and also produce synergistic antitumor responses in combination with chemotherapy. These new immunotoxins have renewed excitement in the field and may prove a promising addition to the targeted therapy repertoire.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland. Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. pastani@mail.nih.gov hassanr@mail.nih.gov.
authors.forename: Raffit
authors.initials: R
authors.lastname: Hassan
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Christine
authors.initials: C
authors.lastname: Alewine
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland. pastani@mail.nih.gov hassanr@mail.nih.gov.
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004195:Disease Models, Animal; D005098:Exotoxins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D008214:Lymphocytes / Q000187:drug effects; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D015649:Pentostatin / Q000627:therapeutic use; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D001427:Bacterial Toxins; D003520:Cyclophosphamide; D005098:Exotoxins; D015649:Pentostatin; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C474515:SS1(dsFv)PE38