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Immunotherapy with anti-GD2 monoclonal antibodies (mAbs) provides some benefits for patients with neuroblastoma (NB). However, the therapeutic efficacy remains limited, and treatment is associated with significant neuropathic pain. Targeting O-acetylated GD2 (OAcGD2) by 8B6 mAb has been proposed to avoid pain by more selective tumor cell targeting. Thorough understanding of its mode of action is necessary to optimize this treatment strategy. Here, we found that 8B6-mediated antibody-dependent cellular phagocytosis (ADCP) performed by macrophages is a key effector mechanism. But efficacy is limited by upregulation of CD47 expression on neuroblastoma cells in response to OAcGD2 mAb targeting, inhibiting 8B6-mediated ADCP. Antibody specific for the CD47 receptor SIRPα on macrophages restored 8B6-induced ADCP of CD47-expressing NB cells and improved the antitumor activity of 8B6 mAb therapy. These results identify ADCP as a critical mechanism for tumor cytolysis by anti-disialoganglioside mAb and support a combination with SIRPα blocking agents for effective neuroblastoma therapy. [ABSTRACT FROM AUTHOR]

Stem cell chemoresistance remains challenging the efficacy of the front‐line temozolomide against glioblastoma. Novel therapies are urgently needed to fight those cells in order to control tumor relapse. Here, we report that anti‐O‐acetyl‐GD2 adjuvant immunotherapy controls glioma stem‐like cell‐driven chemoresistance. Using patient‐derived glioblastoma cells, we found that glioma stem‐like cells overexpressed O‐acetyl‐GD2. As a result, monoclonal antibody 8B6 immunotherapy significantly increased temozolomide genotoxicity and tumor cell death in vitro by enhancing temozolomide tumor uptake. Furthermore, the combination therapy decreased the expression of the glioma stem‐like cell markers CD133 and Nestin and compromised glioma stem‐like cell self‐renewal capabilities. When tested in vivo, adjuvant 8B6 immunotherapy prevented the extension of the temozolomide‐resistant glioma stem‐like cell pool within the tumor bulk in vivo and was more effective than the single agent therapies. This is the first report demonstrating that anti‐O‐acetyl‐GD2 monoclonal antibody 8B6 targets glioblastoma in a manner that control temozolomide‐resistance driven by glioma stem‐like cells. Together our results offer a proof of concept for using anti‐O‐acetyl GD2 reagents in glioblastoma to develop more efficient combination therapies for malignant gliomas. What's new? Glioblastoma multiforme (GBM) is a complex malignancy harboring differentiated tumor‐bulk cells and self‐renewing GBM stem‐like cells (GSCs). Targeting both cell compartments is necessary to improve prognosis. Here, the authors characterize OAcGD2 ganglioside as a novel GSCs marker that sensitizes chemo‐resistant GSCs to TMZ. The combination of anti‐OAcGD2 monoclonal antibody 8B6 with TMZ results in increased temozolomide genotoxicity and tumor cell death in vitro by enhancing temozolomide tumor uptake. Furthermore, 8B6 works synergistically with TMZ to compromise GSCs self‐renewal. The identification of OAcGD2 as a GSC‐associated antigen offers a novel opportunity for optimizing TMZ chemotherapy in GBM patients to prevent recurrence. [ABSTRACT FROM AUTHOR]

Target selection is a key feature in cancer immunotherapy, a promising field in cancer research. In this respect, gangliosides, a broad family of structurally related glycolipids, were suggested as potential targets for cancer immunotherapy based on their higher abundance in tumors when compared with the matched normal tissues. GD2 is the first ganglioside proven to be an effective target antigen for cancer immunotherapy with the regulatory approval of dinutuximab, a chimeric anti-GD2 therapeutic antibody. Although the therapeutic efficacy of anti-GD2 monoclonal antibodies is well documented, neuropathic pain may limit its application. O-Acetyl-GD2, the O-acetylated-derivative of GD2, has recently received attention as novel antigen to target GD2-positive cancers. The present paper examines the role of O-acetyl-GD2 in tumor biology as well as the available preclinical data of anti-O-acetyl-GD2 monoclonal antibodies. A discussion on the relevance of O-acetyl-GD2 in chimeric antigen receptor T cell therapy development is also included. [ABSTRACT FROM AUTHOR]

The uncontrolled disposal of bottom ash generated by the incineration units of hazardous and infected wastes in developed countries are the main cause of significant damage, such as contamination of the soil, as well as surface and underground waters, which may put both the environment and public health at risk. In Morocco, little information is available on the chemical properties of the resulting ashes. In this study, 16 hospital waste ash samples were collected from the incinerators of the two main hospitals in Rabat: Ibn Sina and Cheikh Zayd. A series of tests was conducted, including particle size distribution, mineralogical and chemical composition, and heavy metal leaching behaviour. The results showed that the samples were composed mainly of P2O5 (18%), SiO2 (17%), Na2O (16%), CaO (14%) and SO3 (10%). Moreover, chemical analysis clearly demonstrated that medical waste (MW) contains large amounts of waste generated by domestic activities in the hospital, with a lack of sorting system in the monitoring of MW. Furthermore, the ashes contained high concentrations of heavy metals such as zinc, lead, chromium and nickel with a vast range of 0.5–25071 mg/kg. Leaching tests showed that the extracted amounts of all the heavy metals were lower, with concentrations < 2.85 mg/kg. Comparison of the corresponding heavy metal concentrations with the limit values set by the Council Decision 2003/33/EC allowed us to conclude that bottom ashes meet the waste acceptance criteria regarding these heavy metals. [ABSTRACT FROM AUTHOR]

A "novel" protocol is presented for easy and reliable estimation of soluble hydroxycinnamate levels in Cichorium intybus L. leaf tissue in large-scale experiments. Samples were standardized by punching 6 discs per leaf, and hydroxycinnamates were extracted by submerging the discs in 80% ethanol with 5% acetic acid for at least 48 h in the darkness at 4°C. Residual dry mass of the discs was used for a posteriori correction of compound levels. Chlorophyll was eliminated by chloroform, and the aqueous phases were transferred to microplates, dried, and dissolved in 50% methanol for HPLC analysis and storage. An HPLC program of 8 min was developed for the analysis of the extracts. Comparisons with extractions of liquid nitrogen powders indicated that the novel extraction method was reliable. No degradation of the major hydroxycinnamates-caftaric, chlorogenic, and chicoric acids-was observed, during maceration at ambient temperatures, or after storage for 1 year. [ABSTRACT FROM AUTHOR]