title: Local activation of immune response in bladder cancer patients treated with intraarterial infusion of recombinant interleukin-2.
abstract: Tumor regression induced in cancer patients by i.v. infusion of interleukin-2 (IL-2) is often accompanied by severe side effects. To investigate whether local administration would affect immune response without the side effects, two 5-day cycles of continuous intraarterial [internal iliac artery] infusion of recombinant interleukin-2 (rIL-2) were performed in 12 patients with transitional cell carcinoma (tumor stage 1, node stage 0, metastasis stage 0, and grade 1-2) of the bladder. Four groups of 3 patients were treated at each of 4 escalating doses of rIL-2 (18 x 10(3), 18 x 10(4), 18 x 10(5), and 18 x 10(6) IU/m2/day) throughout the course of the two IL-2 cycles. This treatment was effective in inducing a marked intratumor inflammatory response, consisting mainly of T-lymphocytes and macrophages. A remarkable dose-dependent increase in the levels of soluble CD25 was observed in the urine of all patients, which was associated constantly with an enhanced number of intratumor CD25+ cells. Intratumor macrophages were often immunoreactive for interleukin-1 and/or tumor necrosis factor, suggesting an activated status. Increased levels of soluble CD25 and CD25+ lymphocytes were observed in peripheral blood only at the two highest doses of rIL-2, while increased percentages of circulating HLA-DR+ and CD71+ lymphoid cells and enhancement of CD3+/CD16+ T-lymphocytes were found at lower doses. Peripheral blood eosinophils were augmented in almost all patients but were rarely increased in situ. We provide evidence that continuous intraarterial infusion of rIL-2 activates host immune response, acting preferentially at the tissue level.
authors.affiliation: Department of Experimental Medicine, University La Sapienza, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Velotti
authors.forename: A
authors.initials: A
authors.lastname: Stoppacciaro
authors.forename: L
authors.initials: L
authors.lastname: Ruco
authors.forename: A
authors.initials: A
authors.lastname: Tubaro
authors.forename: A
authors.initials: A
authors.lastname: Pettinato
authors.forename: S
authors.initials: S
authors.lastname: Morrone
authors.forename: T
authors.initials: T
authors.lastname: Napolitano
authors.forename: P C
authors.initials: PC
authors.lastname: Bossola
authors.forename: C R
authors.initials: CR
authors.lastname: Franks
authors.forename: P
authors.initials: P
authors.lastname: Palmer
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004341:Drug Evaluation; D006801:Humans; D007083:Iliac Artery; D007111:Immunity, Cellular; D007261:Infusions, Intra-Arterial; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007962:Leukocytes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy
chemical_list: D015703:Antigens, CD; D007376:Interleukin-2; D011994:Recombinant Proteins