TY - JOUR
T1 - Fresh frozen plasma and platelet concentrates may increase plasma anti-diphtheria toxin IgG concentrations
T2 - Implications for diphtheria fusion protein therapy
AU - Hall, Philip D.
AU - Sinha, Debajyoti
AU - Frankel, Arthur E.
N1 - Funding Information:
Acknowledgements The authors acknowledge the cooperation of the Division of Clinical Pathology in the Department of Pathology and Laboratory Medicine at the Medical University of South Carolina for providing the expired blood products. The authors thank the National Institutes of Health for grant support. The authors also acknowledge the technical assistance of Anne Patala, Christol Cole, McKenzie Turner, Shelly Bratcher, and Robin Minhinnett.
PY - 2006/8
Y1 - 2006/8
N2 - 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-ILS). In trials, patients with anti-DT IgG concentrations >2.5 μg/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 μg/ml (83%), 0.7 μg/ml (83%), and 0.3 μg/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 μg/ ml (86%), 1.9 μg/ml (93%), and 1.4 μg/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 1 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 μg/ml, 0.17 μg/ml, and 0.19 μg/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 μg/ml, 0.06 μg/ml, and 0.07 μg/ml, respectively. In conclusion, a single FFP or PC appears to minimally increase anti-DT IgG concentrations, but multiple units may significantly do such.
AB - 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-ILS). In trials, patients with anti-DT IgG concentrations >2.5 μg/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 μg/ml (83%), 0.7 μg/ml (83%), and 0.3 μg/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 μg/ ml (86%), 1.9 μg/ml (93%), and 1.4 μg/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 1 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 μg/ml, 0.17 μg/ml, and 0.19 μg/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 μg/ml, 0.06 μg/ml, and 0.07 μg/ml, respectively. In conclusion, a single FFP or PC appears to minimally increase anti-DT IgG concentrations, but multiple units may significantly do such.
KW - Anti-DT IgG
KW - Diphtheria fusion proteins
KW - Fresh frozen plasma
KW - Platelet concentrates
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U2 - 10.1007/s00262-006-0124-z
DO - 10.1007/s00262-006-0124-z
M3 - Article
C2 - 16645883
AN - SCOPUS:33646349775
SN - 0340-7004
VL - 55
SP - 928
EP - 932
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 8
ER -