Postchemotherapy and tumor-selective targeting with the La-specific DAB4 monoclonal antibody relates to apoptotic cell clearance

Early identification of tumor responses to treatment is crucial for devising more effective and safer cancer treatments. No widely applicable, noninvasive method currently exists for specifically detecting tumor cell death after cytotoxic treatment and thus for predicting treatment outcomes.

Superior performance of aptamer in tumor penetration over antibody : implication of aptamer-based theranostics in solid tumors

Insufficient penetration of therapeutic agents into tumor tissues results in inadequate drug distribution and lower intracellular concentration of drugs, leading to the increase of drug resistance and resultant failure of cancer treatment. Targeted drug delivery to solid tumors followed by complete drug penetration and durable retention will significantly improve clinical outcomes of cancer therapy. Monoclonal antibodies have been commonly used in clinic for cancer treatment, but their limitation of penetrating into tumor tissues still remains because of their large size. Aptamers, as "chemical antibodies", are 15-20 times smaller than antibodies. To explore whether aptamers are superior to antibodies in terms of tumor penetration, we carried out the first comprehensive study to compare the performance of an EpCAM aptamer with an EpCAM antibody in theranostic applications. Penetration and retention were studied in in vitro three-dimensional tumorspheres, in vivo live animal imaging and mouse colorectal cancer xenograft model. We found that the EpCAM aptamer can not only effectively penetrate into the tumorsphere cores but can also be retained by tumor sphere cells for at least 24 h, while limited tumor penetration by EpCAM antibody was observed after 4 h incubation. As observed from in vivo live animal imaging, EpCAM aptamers displayed a maximum tumor uptake at around 10 min followed by a rapid clearance after 80 min, while the signal of peak uptake and disappearance of antibody appeared at 3 h and 6 h after intravenous injection, respectively. The signal of PEGylated EpCAM aptamers in xenograft tumors was sustained for 26 h, which was 4.3-fold longer than that of the EpCAM antibody. Consistently, there were 1.67-fold and 6.6-fold higher accumulation of PEGylated aptamer in xenograft tumors than that of antibody, at 3 h and 24 h after intravenous administration, respectively. In addition, the aptamer achieved at least a 4-time better tumor penetration in xenograft tumors than that of the antibody at a 200 μm distances from the blood vessels 3 h after intravenous injection. Taken together, these data indicate that aptmers are superior to antibodies in cancer theranostics due to their better tumor penetration, more homogeneous distribution and longer retention in tumor sites. Thus, aptamers are promising agents for targeted tumor therapeutics and molecular imaging.

Middle East respiratory syndrome coronavirus antibody reactors among camels in Dubai, United Arab Emirates, in 2005

We tested, using a low starting dilution, sequential serum samples from dromedary camels, sheep and horses collected in Dubai from February/April to October of 2005 and from dromedary camels for export/import testing between Canada and USA in 2000-2001. Using a standard Middle East respiratory syndrome coronavirus (MERS-CoV) neutralization test, serial sera from three sheep and three horses were all negative while sera from 9 of 11 dromedary camels from Dubai were positive for antibodies supported by similar results in a MERS-CoV recombinant partial spike protein antibody ELISA. The two negative Dubai camels were both dromedary calves and remained negative over the 5 months studied. The six dromedary samples from USA and Canada were negative in both tests. These results support the recent findings that infection with MERS-CoV or a closely related virus is not a new occurrence in camels in the Middle East. Therefore, interactions of MERS-CoV at the human-animal interface may have been ongoing for several, perhaps many, years and by inference, a widespread pandemic may be less likely unless significant evolution of the virus allow accelerated infection and spread potential in the human population.

Characterization of antibody V segment diversity in the Tasmanian devil (Sarcophilus harrisii)

The Tasmanian devil (Sarcophilus harrisii) immune system has recently been under scrutiny because of the emergence of a contagious cancer, which has decimated devil numbers. Here we provide a comprehensive description of the Tasmanian devil immunoglobulin variable regions. We show that heavy chain variable (VH) and light chain variable (VL) repertoires are similar to those described in other marsupial taxa: VL diversity is high, but VH diversity is restricted and belongs only to clan III. As in other mammals, one VH and one Vλ germline family and multiple incomplete Vκ germline sequences were identified in the genome. High Vκ variation was observed in transcripts and we predict that it may have arisen by gene conversion and/or somatic mutations, as it does not appear to have originated from germline variation. Phylogenetic analyses revealed that devil VL gene segments are highly complex and ancient, with some lineages predating the separation of marsupials and eutherians. These results indicate that although the evolutionary history of immune genes lead to the expansions and contractions of immune gene families between different mammalian lineages, some of the ancestral immune gene variants are still maintained in extant species. A high degree of similarity was found between devil and other marsupial VH segments, demonstrating that they originated from a common clade of closely related sequences. The VL families had a higher variation than VH both between and within species. We suggest that, similar to other studied marsupial species, the complex VL segment repertoire compensates for the limited VH diversity in Tasmanian devils.

Efficacy of a parainfluenza virus 5 (PIV5)-based H7N9 vaccine in mice and guinea pigs: antibody titer towards HA was not a good indicator for protection.

H7N9 has caused fatal infections in humans. A safe and effective vaccine is the best way to prevent large-scale outbreaks in the human population. Parainfluenza virus 5 (PIV5), an avirulent paramyxovirus, is a promising vaccine vector. In this work, we generated a recombinant PIV5 expressing the HA gene of H7N9 (PIV5-H7) and tested its efficacy against infection with influenza virus A/Anhui/1/2013 (H7N9) in mice and guinea pigs. PIV5-H7 protected the mice against lethal H7N9 challenge. Interestingly, the protection did not require antibody since PIV5-H7 protected JhD mice that do not produce antibody against lethal H7N9 challenge. Furthermore, transfer of anti-H7 serum did not protect mice against H7N9 challenge. PIV5-H7 generated high HAI titers in guinea pigs, however it did not protect against H7N9 infection or transmission. Intriguingly, immunization of guinea pigs with PIV5-H7 and PIV5 expressing NP of influenza A virus H5N1 (PIV5-NP) conferred protection against H7N9 infection and transmission. Thus, we have obtained a H7N9 vaccine that protected both mice and guinea pigs against lethal H7N9 challenge and infection respectively.

Aptamers: a promising chemical antibody for cancer therapy

Aptamers, also known as chemical antibodies, are single-stranded nucleic acid oligonucleotides which bind to their targets with high specificity and affinity. They are typically selected by repetitive in vitro process termed systematic evolution of ligands by exponential enrichment (SELEX). Owing to their excellent properties compared to conventional antibodies, notably their smaller physical size and lower immunogenicity and toxicity, aptamers have recently emerged as a new class of agents to deliver therapeutic drugs to cancer cells by targeting specific cancer-associated hallmarks. Aptamers can also be structurally modified to make them more flexible in order to conjugate other agents such as nano-materials and therapeutic RNA agents, thus extending their applications for cancer therapy. This review presents the current knowledge on the practical applications of aptamers in the treatment of a variety of cancers.