title: Interleukin-2 receptor-directed therapies: antibody-or cytokine-based targeting molecules.
abstract: With the exception of certain hematologic malignancies, the high affinity interleukin-2 (IL-2) receptor is only transiently expressed during the brief antigen-triggered proliferative burst of lymphocytes. Hence, we wondered whether administration of anti-IL-2 receptor (IL-2R) monoclonal antibody (mAb) or chimeric IL-2 toxins would provide a utilitarian way to achieve immunosuppression aimed directly at activated lymphocytes, or whether this approach could be used to treat IL-2R+ leukemia/lymphoma. Studies in preclinical autoimmune and transplant models indicate that this approach can be effective. The results of open, uncontrolled studies provide preliminary evidence that a chimeric IL-2 toxin is well tolerated at doses that may induce improvement in patients with IL-2R+ leukemia/lymphoma, as well as in patients with refractory rheumatoid arthritis or new-onset diabetes mellitus.
authors: Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors: T B
authors: TB
authors: Strom
authors: V R
authors: VR
authors: Kelley
authors: J R
authors: JR
authors: Murphy
authors: J
authors: J
authors: Nichols
authors: T G
authors: TG
authors: Woodworth
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C054780:DAB(486)-interleukin 2; D004167:Diphtheria Toxin; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins