No abstract

Developing potent adjuvants for the stimulation of robust immune response is central for effective cancer immunotherapy. Double-shelled dendritic mesoporous organosilica hollow spheres are an excellent adjuvant and provide superior immunity in cancer immunotherapy, and better than their counterparts either with a pure silica composition or a single-walled architecture. This study provides new insights in the rational design of effective nanostructured adjuvants for vaccine developments.

Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug via a chemical linker. After decades of preclinical and clinical studies, a series of ADCs have been widely used for treating specific tumor types in the clinic such as brentuximab vedotin (Adcetris®) for relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, gemtuzumab ozogamicin (Mylotarg®) for acute myeloid leukemia, ado-trastuzumab emtansine (Kadcyla®) for HER2-positive metastatic breast cancer, inotuzumab ozogamicin (Besponsa®) and most recently polatuzumab vedotin-piiq (Polivy®) for B cell malignancies. More than eighty ADCs have been investigated in different clinical stages from approximately six hundred clinical trials to date. This review summarizes the key elements of ADCs and highlights recent advances of ADCs, as well as important lessons learned from clinical data, and future directions.

No abstract

Folate receptors (FRs) have been identified as cellular surface markers for cancer and leukemia. Liposomes containing lipophilic derivatives of folate have been shown to effectively target FRexpressing cells. Here, we report the synthesis of a novel lipophilic folate derivative, folatepolyethylene glycol-cholesterol hemisuccinate (F-PEG-CHEMS), and its evaluation as a targeting ligand for liposomal doxorubicin (L-DOX) in FR-expressing cells. Liposomes containing F-PEG-CHEMS, with a mean diameter of 120±20nm, were synthesized by polycarbonate membrane extrusion and were shown to have excellent colloidal stability. The liposomes were taken up selectively by KB cells, which overexpress FR-α. Compared to folate-PEG-cholesterol (F-PEGChol), which contains a carbamate linkage, F-PEG-CHEMS better retained its FR-targeting activity during prolonged storage. In addition, F-PEG-CHEMS containing liposomes loaded with DOX (F-L-DOX) showed greater cytotoxicity (IC 50 =10.0μM) than non-targeted control L-DOX (IC 50 = 57.5μM) in KB cells. In ICR mice, both targeted and non-targeted liposomes exhibited long circulation properties, although F-L-DOX (t 1/2 = 12.34 hr) showed more rapid plasma clearance than L-DOX (t 1/2 = 17.10 hr). These results suggest that F-PEG-CHEMS is effective as a novel ligand for the synthesis of FR-targeted liposomes. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. , 2001; Momot et al., 2003;Papahadjopoulos et al., 1991) and is facilitated by plasma protein opsonization. Incorporation of polyethylene glycol (PEG) coating on liposomes has been shown to reduce the rate of RES clearance of liposomes Fritze et al., 2006; Momot et al., 2003;Papahadjopoulos et al., 1991). Liposomal delivery has been shown to reduce cardiac toxicity of doxorubicin (Perez et al., 2002). Targeted liposomes can be synthesized by incorporating a tumor cell-selective ligand, such as antibodies, transferrin and folic acid (Gabizon et al., 2004;Lukyanov et al., 2004;Pan et al. 2007;Wu et al., 2006a;Xiong et al., 2005), via a lipophilic anchor, typically consisting of a derivative of distearoylphosphatidylethanolamine (DSPE). NIH Public AccessMembrane folate receptors (FRs), including FR-α and FR-β, are glycosylphosphatidylinositol (GPI)-anchored glycoproteins. FR-α expression is amplified in over 90% of ovarian carcinomas and at varying frequencies in other epithelial cancers. Meanwhile, FR-β is expressed in a non-functional form in neutrophils and in a functional form in activated macrophages and in myeloid leukemias (Elwood et al., 1989;McHugh et al., 1979). In contrast, most normal...