A repertoire of cytotoxic payloads is increasing

A repertoire of cytotoxic payloads is increasing; among those, MMAE has been utilized for the highly effective ADC brentuximab vedotin. However, the ADCs which utilized MMAE to target GCC in solid tumors have shown a poor efficacy suggesting that various tumor types respond differently to a given toxic agent which is similar to conventional chemotherapy drugs. In addition, intratumoral heterogeneity within the tumor as well as clonal expansion of resistant cells may contribute to resistance of ADCs (Gerlinger et al., 2012). Determining the optimal drug-to-antibody ratio (DAR) is another area of further exploration. The DAR is highly dependent on other ADC variables; however, multiple ADCs are showing DAR close to 4 (Hamblett et al., 2004, Teicher and Chari, 2011). Finally, the relationship between GCC expression in primary and metastatic sites as well as the effects of multiple lines of therapy on GCC expression is also under investigation.
Conclusion
Conflict of interest
Introduction The importance of intestinal health has been recognized for over 2000years, most famously by Hippocrates who said, “All disease begins in the gut”. Although not every disease may initiate in the intestine, overall human health and well-being is strongly dependent on the integrity of the gastrointestinal (GI) tract. The GI tract is the largest organ-system in the body, and is responsible for the ingestion, digestion and assimilation of food for the survival of the organism. In this process the digestive system also has to adapt to a large number of microbes that are ingested with the food and colonize the intestine [1]. There are several defence strategies employed by the GI tract to achieve this, which include the secretion of antibodies in the mouth [2], the acidic pH in the stomach, and cellular defence mechanisms that operate within the intestine [3]. The intestine is the major site of digestion and 50 dub of nutrients. Therefore, to enhance the surface area and thus the absorptive capacity, intestinal villi form finger-like projections into the lumen of the intestine. The villi are separated from each other by crypts [4]. Epithelial cells that line the intestine are primarily comprised of enterocytes which are absorptive in function [5]. The enterocytes are polarized whereby the cell membrane is distinctly sectioned into an apical and basolateral region, separated by tight junctions. Other specialized cells present in the GI tract include goblet cells which secrete mucous and other glycoproteins, the enteroendocrine cells which secrete hormones, the dendritic cells which are antigen presenting cells, the M-cells or microfold cells which are responsible for antigen sampling, and the Paneth cells, which are found in the crypts and produce antibacterial peptides [3]. Located at the base of the crypt are the intestinal stem cells that provide daughter transit amplifying cells that ultimately form all the differentiated cells of the intestine [6]. The epithelial layer of cells is protected from the contents of the lumen by a thick mucosal layer made up of glycoproteins and mucins, which can contain antibodies and antimicrobial peptides. The human gut is a rich source of nutrition and plays host to a variety of microbes that co-exist with a mutual dependence called commensalism. The microbiome is comprised mainly of bacteria [3], some protozoans [7] and even fungi [8]. They contribute to host nutrition by producing enzymes that breakdown complex polysaccharides for efficient digestion of ingested food, and by producing metabolites such as vitamins [9]. These microbes do not disrupt the normal physiology of the body and their numbers are kept in check by basal immune activity, which is stimulated by factors such as peptidoglycans from the bacterial cell wall [10]. Genetic variation in humans give rise to differences in their immune system, which then reflects in the composition of the microbiota, and these differences are being correlated to the susceptibility of the individual to immune-related diseases such as asthma and intestinal inflammation [3].