title: Effects of an anti-CD5 immunoconjugate (CD5-plus) in recent onset type I diabetes mellitus: a preliminary investigation. The CD5 Diabetes Project Team.
abstract: Type-I (insulin-dependent) diabetes mellitus is an immunologically mediated disease that results in destruction of the insulin secreting beta cells of the pancreas. T cells have been implicated in the pathogenesis of this disease. One novel form of anti-T-cell therapy is the immunoconjugate CD5-Plus. This agent is composed of the murine IgG1 monoclonal antibody H65, which is directed toward the CD5+ antigen; and ricin A chain, a ribosomal inhibitor protein. We performed a pilot study to evaluate the safety of the immunoconjugate in subjects with type-I diabetes mellitus. We conducted a dose-escalation study using CD5-Plus given as an intravenous infusion for 5 consecutive days. Fifteen subjects (12 men and 3 women) with a mean age of 26 years, a mean duration of diabetes of 4.8 months, and a minimum stimulated C peptide of 0.3 pmol/mL were entered. Six subjects each were treated at the 0.1 and 0.2 mg/kg/day dosage levels, and three subjects were treated at the 0.33 mg/kg/day dose. Glycemic control was determined monthly by recording the glycohemoglobin, total daily insulin requirements, and fasting blood glucoses. Beta-cell function was measured by determining the C-peptide response to a mixed formula meal (Sustacal) at baseline and at 1,3,6,9, and 12 months after treatment. The area under the curve (AUC) of the C-peptide response was calculated and, to reduce variability, related to that of the same subject at baseline. An analysis of subjects who retained at least 80% of their baseline beta-cell function as measured by the AUC was performed.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University of Miami School of Medicine, Florida 33101.
authors.forename: J S
authors.initials: JS
authors.lastname: Skyler
authors.forename: T J
authors.initials: TJ
authors.lastname: Lorenz
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: G S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: D
authors.initials: D
authors.lastname: Einhorn
authors.forename: J P
authors.initials: JP
authors.lastname: Palmer
authors.forename: J B
authors.initials: JB
authors.lastname: Marks
authors.forename: C
authors.initials: C
authors.lastname: Greenbaum
authors.forename: E A
authors.initials: EA
authors.lastname: Saria
authors.forename: V
authors.initials: V
authors.lastname: Byers
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000097:blood / Q000276:immunology*; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D018956:CD5 Antigens; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use / Q000633:toxicity*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008212:Lymphocyte Depletion; D008297:Male; D012044:Regression Analysis; D012276:Ricin / Q000627:therapeutic use / Q000633:toxicity*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002096:C-Peptide; D018956:CD5 Antigens; D000922:Immunotoxins; D007328:Insulin; D012276:Ricin