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Peptide Alone (peptide + alone)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2005
Kristin Hochweller
Abstract Steady-state dendritic cells (DC) present peptide-MHC complexes to T cells in a tolerogenic manner, presumably because of deficient costimulation. However, it is clear that the path to tolerance involves initial T cell activation, suggesting that the deficit may lie in late-acting costimulatory molecules. With this in mind we have investigated the kinetics of expression of several costimulatory pairs on DC and OVA-reactive T cells after i.v. injection of mice with peptide and LPS (immunity), or peptide alone (tolerance). We find that T cells up-regulate CD154, OX40, RANKL and PD-1 whether they are destined for tolerance or immunity, although there are some differences in the levels and length of expression. In contrast, when analyzing DC, we found that up-regulation of CD80, CD86, CD40, RANK and PDL-1 occurred only when peptide was co-administered with LPS. These data give a picture of the T cell looking for costimulatory cues that are not forthcoming when pMHC is presented by steady-state DC, leading to tolerance. However, we did see a strong and rapid up-regulation of RANKL on T cells that occurred specifically when peptide was given in the absence of LPS, suggesting a possible positive signal influencing the decision between tolerance and immunity. [source]

Production of a recombinant cholera toxin B subunit-insulin B chain peptide hybrid protein by Brevibacillus choshinensis expression system as a nasal vaccine against autoimmune diabetes

BIOTECHNOLOGY & BIOENGINEERING, Issue 7 2005
Yoshikazu Yuki
Abstract Mucosally induced tolerance is an attractive strategy for preventing or reducing autoimmune diseases. Here, we produced a recombinant CTB fusion protein linked with autoantigen T cell epitope of insulin B chain peptide 9,23 (C19S) at levels up to 200 mg/L culture media in Brevibacillus choshinensis secretion-expression system. Receptor-competitive assay showed that the CTB-insulin peptide binds to GM1 receptor almost equivalent degree as the native form of CTB. Non-obese diabetes (NOD) mice that spontaneously develop an insulin-dependent diabetes were nasally immunized with CTB-insulin peptide (5 µg) for three times. The nasal treatment significantly reduced the development of insulin-dependent diabetes and peptide specific DTH responses after systemic immunization with the insulin peptide B 9,23(C19S) in CFA. Nasal administration of as high as 50 µg of the peptide alone demonstrated a similar level of the disease inhibition. In contrast, all mice given 5 µg of the insulin peptide alone or 5 µg of insulin peptide with 25 µg of the free form of CTB did not lead to the suppression of diabetes development and DTH responses. Because molecular weight of the insulin peptide is about one tenth of that of the CTB-insulin peptide, the results demonstrate that the recombinant hybrid of autoantigen and CTB increased its tolerogenic potential for nasal administration by up 100-fold on molar base of autoantigen peptide. Taken together, nasally-induced tolerance by administration of the recombinant B.choshinensis -derived hybrid protein of CTB and autoantigen T cell-epitope peptide could be useful mucosal immunetherapy for the control of T cell-mediated autoimmune diseases. © 2005 Wiley Periodicals, Inc. [source]

Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab,)2 antibody,,

CANCER, Issue S4 2010
Frits Aarts PhD
Abstract BACKGROUND: Antibody-based imaging agents are available commercially, but their success has been limited, mainly because of low contrast and the emergence of 2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scanning. In pretargeting, administration of the radionuclide is separated from the antibody, thereby enhancing image contrast and allowing detection at earlier time points after injection. METHODS: The authors conducted an open-label, single-arm trial that assessed a pretargeting procedure in which an anticarcinoembryonic antigen x (anti-CEA x) anti-diethylenetriaminepentaacetic acid (anti-DTPA)-indum (In) antibody was used in combination with a 111In-labeled di-DTPA peptide for the diagnostic imaging of CEA-expressing colorectal cancer. Three patients received the 111In peptide alone to investigate tumor targeting, organ distribution, and clearance of the peptide. Thereafter, 11 patients received the bispecific antibody (bsAb) (5 mg) to pretarget the tumor. After 3 to 5 days, patients were injected with 185 megabecquerels of 111In-labeled peptide to assess the optimal interval for best image quality. RESULTS: Fourteen patients with primary colorectal cancer were enrolled. One of 3 patients who received 111In peptide alone had low-level tumor uptake. In 9 of 11 other patients, tumors were observed. In 1 patient, FDG-PET,positive lymph nodes were observed clearly with pretargeted immunoscintigraphy. Peptide pharmacokinetics revealed enhanced circulating levels of 111In-labeled peptide in patients in the 3-day interval cohort compared with the other cohorts. Tumor-to-background ratios ranged from 3.5 to 6.4 in the 3-day interval group, from 5.1 to 14.2 in the 4-day interval group, and from 3.5 to 3.9 in the 5-day interval group. The best images were acquired with a 4-day interval at 24 hours after injection of the radiolabeled peptide. Grade 1 adverse events were observed in 2 patients. CONCLUSIONS: Imaging of colorectal cancer using a 2-step, pretargeting system produced the best imaging results 24 hours after peptide administration using a 4-day interval between injection of the bsAb and the peptide. Cancer 2010;116(4 suppl):1111,7. © 2010 American Cancer Society. [source]