Engineering the First Chimeric Antibody in Targeting Intracellular PRL-3 Oncoprotein for Cancer Therapy in Mice

Antibodies are considered as ‘magic bullets’ because of their high specificity. It is believed that antibodies are too large to routinely enter the cytosol, thus antibody therapeutic approach has been limited to extracellular or secreted proteins expressed by cancer cells. However, many oncogenic proteins are localized within the cell. To explore the possibility of antibody therapies against intracellular targets, we generated a chimeric antibody targeting the intracellular PRL-3 oncoprotein to assess its antitumor activities in mice. Remarkably, we observed that the PRL-3 chimeric antibody could efficiently and specifically reduce the formation of PRL-3 expressing metastatic tumors. We further found that natural killer (NK) cells were important in mediating the therapeutic effect, which was only observed in a nude mouse model (T-cell deficient), but not in a Severe Combined Immunodeficiency’ (scid) mouse model (B- and T-cell deficient), indicating the anticancer effect also depends on host B-cell activity. Our study involving 377 nude and scid mice suggests that antibodies targeting intracellular proteins can be developed to treat cancer

Evaluation of acute and subacute toxicity of Vernonia cinerea (L.) Less using mice model

270-277Vernonia cinerea (L.) Less is a medicinal plant distributed throughout India and is used traditionally for treating several diseases. This study aimed to analyze the toxicological effects of ethyl acetate extract (VCEA) of this plant. Preliminary phytochemical screening of VCEA was conducted by conventional methods. For acute toxicity studies, female Swiss albino mice were treated with a single oral dose of 2000 mg/kg body weight of VCEA and observed for any changes in general characters. For the subacute toxicity study, mice were treated (50 or 100 mg/kg body weight) consecutively for 28 days and the haematological, biochemical, and histopathological changes were analysed. From the phytochemical analysis, it was inferred that terpenoid content was more in the VCEA extract. No mortality or toxic effects were observed in the acute study. Repeated dosage of VCEA at 50 mg/kg body weight did not impart any adverse effects in any of the parameters assessed. The higher dosage (100 mg/kg body weight) made the animals slightly anaemic. Therefore a dose of up to 50 mg/kg body weight is recommended as safe for testing the pharmacological properties of VCEA in mice models

Engineering the First Chimeric Antibody in Targeting Intracellular PRL-3 Oncoprotein for Cancer Therapy in Mice

10.18632/oncotarget.442ONCOTARGET32158-171United State