Purpose: CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein
belonging to the B7 receptor family present on lymphocytes. The ...objectives of this phase I study were to assess the dose-limiting
toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients
with advanced hematologic malignancies.
Experimental Design: Seventeen patients were treated with escalating doses of CT-011 ranging from 0.2 to 6 mg/kg. For pharmacokinetic analysis,
blood samples were withdrawn from the patients before and immediately after treatment and at 24 hours, 48 hours, and on days
7, 14, and 21. CT-011 blood levels were assessed with a specific ELISA and derived concentrations were used to calculate pharmacokinetic
parameters. Activation of the immune system was assessed by measuring peripheral blood CD4 + , CD8 + , and CD69 + lymphocytes.
Results: The study showed the antibody to be safe and well tolerated in this patient population. No single maximum tolerated dose
was defined in this study. Clinical benefit was observed in 33% of the patients with one complete remission. Pharmacokinetic
analyses show that serum C max and the AUC of CT-011 increased proportionally with dose. The median t 1/2 of CT-011 ranged from 217 to 410 hours. Sustained elevation in the percentage of peripheral blood CD4 + lymphocytes was observed up to 21 days following CT-011 treatment.
Conclusions: A single administration of 0.2 to 6.0 mg/kg of CT-011 is safe and well tolerated in patients with advanced hematologic malignancies.
The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in ...the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-γin vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV.
Porous materials such as cellular cytosol, hydrogels, and block copolymers have nanoscale features that determine macroscale properties. Characterizing the structure of nanopores is difficult with ...current techniques due to imaging, sample preparation, and computational challenges. We produce a super-resolution optical image that simultaneously characterizes the nanometer dimensions of and diffusion dynamics within porous structures by correlating stochastic fluctuations from diffusing fluorescent probes in the pores of the sample, dubbed here as “fluorescence correlation spectroscopy super-resolution optical fluctuation imaging” or “fcsSOFI”. Simulations demonstrate that structural features and diffusion properties can be accurately obtained at sub-diffraction-limited resolution. We apply our technique to image agarose hydrogels and aqueous lyotropic liquid crystal gels. The heterogeneous pore resolution is improved by up to a factor of 2, and diffusion coefficients are accurately obtained through our method compared to diffraction-limited fluorescence imaging and single-particle tracking. Moreover, fcsSOFI allows for rapid and high-throughput characterization of porous materials. fcsSOFI could be applied to soft porous environments such hydrogels, polymers, and membranes in addition to hard materials such as zeolites and mesoporous silica.
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