Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

Adoptive therapy of malignant diseases with cytokine-induced killer (CIK) cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR) with an antibody-defined specificity for carcinoembryonic antigen (CEA). CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions

Adsorption calorimetric study of the organization of sodium n-decyl sulfate at the graphite/solution interface

The material and enthalpy balances of the adsorption of sodium n-decyl sulfate from aqueous solutions onto graphitized carbon black were determined between 288 and 318 K by using an automated flow sorption/microcalorimeter system. At low concentrations, the surfactant molecules form a flat monomolecular film on the graphite plane, in consequence of surface-directed ordering. A mechanism is proposed in which two adsorbed phases coexist during the formation of this surfactant monolayer. The enthalpy of adsorption in the monolayer region is ca. -42 kJ mol(-1), which does not depend appreciably on the temperature or on the surface coverage. At higher concentrations, the ordered monolayer induces surface aggregation to produce half-cylindrical hemimicelles as the critical micelle concentration is approached. The enthalpies of surface aggregation at 288, 298, and 318 K are -10, -16, and -26 kJ mol(-1), respectively. As the temperature is increased from 288 to 318 K, the average number of surfactant molecules in the cross section of a half-cylinder drops from ca. 5.4 to 3.4. Calorimetric evidence is provided that cationic and anionic surfactant adsorption on graphite follow the same mechanism in the low-density and high-density adsorbate regions

Description and evaluation of a sampling system for long-time monitoring of PAHs wet deposition

In this paper a new electronically controlled year-round wet-only sampler for wet deposition of trace organic compounds (e.g. airborne PAHs) is described. The sampler provides in situ filtration of the precipitation as well as preconcentration of nonpolar organic compounds by means of a C18-PAH modified silica gel cartridge. The whole assembly is insulated and equipped with heating elements which permit collection of wet deposition as ice or snow and insure correct function of the sampling system even during cold weather. Concurrent chemical analysis of both the particulate and the dissolved phases is performed by high resolution gas chromatography with flame ionization detection or HPLC with fluorescence detection. The reliability of the method was proved by analyzing PAH spiked water (simulated rain) and using NIST SRM 1649 ('urban dust') as certified material for particle-bound PAHs in precipitation. This study proved satisfactorily recoveries of as both particle-bound and unbound aqueous PAH, with only small losses to collector surfaces. It was proved that this new wet-only precipitation sampler can successfully be used for long-time monitoring of PAH in wet depositions in urban areas. (C) 2002 Elsevier Science Ltd. All rights reserved

A recombinant anti‐carcinoembryonic antigen immunoreceptor with combined CD3ζ‐CD28 signalling targets T cells from colorectal cancer patients against their tumour cells

BACKGROUND AND AIMS: The prognosis of metastatic colorectal cancer is still poor, raising the need for alternative therapeutic approaches, particularly by manipulating the antitumour immune response. Advanced tumour stages, however, are frequently accompanied by functional T cell defects which may be critical for a T cell based anticancer immunotherapy. The aim of this study was to address whether T cells from colorectal cancer patients with advanced tumour stages can be specifically antigen activated against their autologous tumour cells. METHODS: T cells were isolated from colorectal cancer patients and retrovirally transduced to express a recombinant immunoreceptor that has an extracellular binding domain for carcinoembryonic antigen (CEA) and an intracellular CD3ζ signalling domain with and without CD28 costimulation for T cell activation. RESULTS: Peripheral blood T cells from colorectal cancer patients were successfully engineered to express the anti‐CEA immunoreceptor on the cell surface. On coincubation with autologous CEA(+) tumour cells, T cells with anti‐CEA immunoreceptor are specifically activated to secrete interferon γ (IFN‐γ) and to lyse autologous tumour cells whereas T cells without immunoreceptor are not. T cells equipped with combined CD3ζ‐CD28 signalling receptor are more efficiently activated to secrete IFN‐γ compared with T cells with CD3ζ signalling receptor. Induction of interleukin 2 secretion on targeting towards autologous tumour cells requires triggering of T cells by the CD3ζ‐CD28 costimulatory receptor. CONCLUSIONS: T cells from advanced colorectal cancer patients can be tumour specifically activated with high efficiency by engraftment with a combined CD3ζ‐CD28 immunoreceptor to break tolerance against autologous tumour cells