Undergraduate Student, Level IV
I am enrolled in Honours Life Sciences, year four, in the Faculty of Science. I have always been fond of our immune system and its capability to combat pathogens in our body. Natural killer (NK) cells have been a special interest of mine due to their ability to kill tumor cells and virus-infected cells without previous immune priming.
Natural killer cells are constituents of the innate immune system having the ability to release cytotoxic granules to lyse their targets. In the past, it was found that antibodies are able to mediate and enhance the ability for natural killer cells to lyse their target cells, a process termed antibody dependent cellular cytotoxicity (ADCC). This is done when the antibody binds to an abundant receptor/antigen on the tumor cell at one end, and on the other binds the Fc segment to the CD16 receptor on NK cells to mediate cellular toxicity. Studies using natural killer cells and ADCC have shown promising results in vitro, however, their impact has been thwarted in vivo due to the restricting tumor microenvironment, in particular, due to the hypoxic conditions. Fortunately, recent experiments from the Ashkar Lab among others, have shown that expanding natural killer cells in presence of interleukin-21 allows NK cells to function in tumor microenvironments as well as enhance their cytotoxicity function.
My project specifically focuses on engineering an antibody most effective with expanded NK cells to render efficient ADCC, especially when placed in inhibiting environments. NK cell cytotoxicity will be compared with and without the presence of the engineered antibody. If deemed effective, my goal will be to establish human cell lines that permanently express our antibody, and pursuing in vivo experiments as well as clinical trials.
This research is supported by the Natural Sciences and Engineering Research Council of Canada Undergraduate Student Research Award (NSERC USRA).