title: Fresh frozen plasma and platelet concentrates may increase plasma anti-diphtheria toxin IgG concentrations: Implications for diphtheria fusion protein therapy.
abstract: We are developing two fusion proteins consisting of a diphtheria toxin (DT) linked to either granulocyte macrophage colony stimulating factor (DT388-GMCSF) or interleukin-3 (DT388-IL3). In trials, patients with anti-DT IgG concentrations >2.5 microg/ml had significantly lower concentrations of either fusion protein. DT389-IL2 is currently FDA approved for the treatment of cutaneous T-cell lymphomas. We noted increased concentrations of anti-DT IgG after administration of platelet concentrates (PC). Because many of these patients require transfusions, we measured the anti-DT IgG content of FFP and PC. We assayed 14 bags of FFP and 12 bags of single-donor PCs for anti-DT IgG by an enzymoimmunoassay against DT389-IL2, DT388-IL3, DT388-GMCSF. The median (percent of samples positive) of anti-DT IgG concentrations in PC against DT388-GMCSF, DT388-IL3, DT389-IL2 was 0.8 microg/ml (83%), 0.7 microg/ml (83%), and 0.3 microg/ml (58%), respectively. The median (percent of samples positive) anti-DT IgG concentration in FFP against DT388-GMCSF, DT388-IL3, and DT389-IL2 was 2.1 microg/ml (86%), 1.9 microg/ml (93%), and 1.4 microg/ml (86%), respectively. There was a strong association between anti-DT389IL2 IgG, anti-DT388IL3 IgG, and anti-DT388GMCSF IgG concentrations in both the FFP (95.6%) and PC (76.3%). Assuming a plasma volume of 3 l in a 70 kg patient, a single FFP unit would increase the plasma anti-DT389IL2 IgG, anti-DT388IL3 IgG, and anti-DT388GMCSF IgG by 0.13 microg/ml, 0.17 microg/ml, and 0.19 microg/ml, respectively. For PC, a single unit would increase plasma anti-DT389-IL2 IgG, anti-DT388-IL3 IgG, and anti-DT388-GMCSF IgG by 0.03 microg/ml, 0.06 microg/ml, and 0.07 microg/ml, respectively. In conclusion, a single FFP or PC appears to minimally increase anti-DT IgG concentrations, but multiple units may significantly do such.
authors.affiliation: Department of Pharmacy, The Medical University of South Carolina, and the Cancer Research Institute, Scott and White Memorial Hospital, 280 Calhoun Street, Box 250142, Charleston, SC 29425, USA. hallpd@musc.edu
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hall
authors.forename: Debajyoti
authors.initials: D
authors.lastname: Sinha
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Frankel
mesh_terms: D001792:Blood Platelets; D019496:Cancer Vaccines / Q000276:immunology*; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D000922:Immunotoxins / Q000097:blood; D007376:Interleukin-2 / Q000276:immunology; D007377:Interleukin-3 / Q000276:immunology; D007938:Leukemia / Q000628:therapy; D010949:Plasma; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000627:therapeutic use; D011994:Recombinant Proteins
chemical_list: D019496:Cancer Vaccines; D004167:Diphtheria Toxin; D007074:Immunoglobulin G; D000922:Immunotoxins; D007376:Interleukin-2; D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor