Search

Whereas cancers grow within host tissues and evade host immunity through immune-editing and immunosuppression (1-5), tumours are rarely transmissible between individuals. Much like transplanted allogeneic organs, allogeneic tumours are reliably rejected by host T cells, even when the tumour and host share the same major histocompatibility complex alleles, the most potent determinants of transplant rejection (6-10). How such tumour-eradicating immunity is initiated remains unknown, although elucidating this process could provide the basis for inducing similar responses against naturally arising tumours. Here we find that allogeneic tumour rejection is initiated in mice by naturally occurring tumour-binding IgG antibodies, which enable dendritic cells (DCs) to internalize tumour antigens and subsequently activate tumour-reactive T cells. We exploited this mechanism to treat autologous and autochthonous tumours successfully. Either systemic administration of DCs loaded with allogeneic-IgG-coated tumour cells or intratumoral injection of allogeneic IgG in combination with DC stimuli induced potent T-cell-mediated antitumour immune responses, resulting in tumour eradication in mouse models of melanoma, pancreas, lung and breast cancer. Moreover, this strategy led to eradication of distant tumours and metastases, as well as the injected primary tumours. To assess the clinical relevance of these findings, we studied antibodies and cells from patients with lung cancer. T cells from these patients responded vigorously to autologous tumour antigens after culture with allogeneic-IgG-loaded DCs, recapitulating our findings in mice. These results reveal that tumour-binding allogeneic IgG can induce powerful antitumour immunity that can be exploited for cancer immunotherapy., To study the basis of allogeneic tumour rejection, we examined the immune response to tumours in major histocompatibility complex (MHC)-matched allogeneic mice (illustrated in Fig. 1a). B16 melanoma cells expanded [...]

Chronic inflammation characterized by T cell and macrophage infiltration of visceral adipose tissue (VAT) is a hallmark of obesity-associated insulin resistance and glucose intolerance. Here we show a fundamental pathogenic role for B cells in the development of these metabolic abnormalities. B cells accumulate in VAT in diet-induced obese (DIO) mice, and DIO mice lacking B cells are protected from disease despite weight gain. B cell effects on glucose metabolism are mechanistically linked to the activation of proinflammatory macrophages and T cells and to the production of pathogenic IgG antibodies. Treatment with a B cell-depleting CD20 antibody attenuates disease, whereas transfer of IgG from DIO mice rapidly induces insulin resistance and glucose intolerance. Moreover, insulin resistance in obese humans is associated with a unique profile of IgG autoantibodies. These results establish the importance of B cells and adaptive immunity in insulin resistance and suggest new diagnostic and therapeutic modalities for managing the disease., Obesity and its associated metabolic abnormalities, including insulin resistance and type 2 diabetes, have reached epidemic proportions, adversely affecting health and global mortality rates (1). Multiple factors contribute to reduced [...]

The synthesis and characterization of seven new titanium catechol-based complexes are reported. The results have shown that a coordinated 2-propanol is observed in all the structures, which is involved in hydrogen bonding to one of the isopropoxide ligands, and the complexes are screened for the ring-opening polymerization (ROP) of epsilon-caprolactone at room temperature.

A cationic aminophenoxy-aluminium compound has been synthesized and its solid-state structure analyzed. Four H2salen aluminium derivatives have also been synthesized and structurally analyzed. The derivatives have varying counterions. Dimer formation via weak NH hydrogen bonded Cl- ions is found in three of the compounds. Ionic lattice-type structures are found in the rest.

The bis-guanidino compound [H.sub.2]C[{hpp}.sub.2] (hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) is converted to the monocation and isolated as the chloride and tetraphenylborate salts. Triadic analysis has shown that the dominant term causing the high basicity is the relaxation energy.

The analysis describes the synthesis, characterization and the structure of a molecular trinuclear barium aminebis(phenolate) complex. The results show that the complex can be easily used as an initiator for the ring-opening polymerization of several cyclic esters.

An air-stable titanium-organic framework, prepared from Ti(OPr)4 and 1,4-butanediol, is characterized through single-crystal X-ray diffraction, revealing a unique supermolecular structure. Its functionality as a high active initiator for the ring-opening polymerization of cyclic esters is also demonstrated.

The application of aminetris(phenoxide) ligands to Bi and Sb chemistry, resulting in the structural characterization of an isolated Bi 'inverted-sandwich' complex, which is well-defined and hydrocarbon-soluble, is reported. The density functional theory calculations of the sandwich bismuth arene complex have indicated the presence of a weak sigma*-2pi interaction.

The chiral fluorescent sensor was found to be highly sensitive, chemeoselective and enantioselective to sugar acids, such as tartic acid, glucaric acid, and gluconic acid. The results and the unambiguous structural data could be useful for the development and application of enantioselective chemical sensors.

Phenol.nitroxide radicals were studied using neutron diffraction, as a model for hydrogen atom abstraction by peroxyl radicals.