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Expansion of Highly Cytotoxic Human Natural Killer Cells by Osteoclast for Cancer Immunotherapy

  • Author(s): Park, So-Hyun
  • Advisor(s): Jewett, Anahid
  • et al.
Abstract

Natural Killer (NK) cells have a crucial role in immune surveillance against a variety of infectious microorganisms and tumors. NK cells are known to mediate direct cytotoxicity as well as antibody dependent cellular cytotoxicity (ADCC) against a variety of tumor cells. Also, they are known to regulate the functions of other cells by producing key cytokines and chemokines. In the tumor microenvironment, cytotoxic function of NK cells is suppressed by a number of distinct effectors and their secreted factors. It has been shown that many cancer patients have decreased peripheral blood NK cell function, so NK cell-based immunotherapy has been used as a treatment in order to enhance NK cell function. However, limited availability of NK cells and ability to expand has restricted development of NK cell immunotherapy. Overcoming NK cell tolerance against tumors by developing new ways of activating endogenous NK cells that increase the expression of ligands for activating NK cell receptors or that render them more sensitive to NK cell mediated killing is crucial.

In this study, we found the novel way to expand NK cells and the functionality of NK cells generated under this condition demonstrated enhanced expression of activating NK receptors. Also, significant cytotoxic killing potential after culture was discovered as well as augmented cytokine secretion. Therefore, these expanded NK cells are highly functional in comparison to primary NK cells. Through the help of cytokines, sAJ2 bacteria and osteoclast, NK cells can be expanded and activated in vitro and furthermore, these expanded NK cells can be used to target tumors in vivo. Expanded NK cells can be used in combination with other treatment modalities, potentially leading to synergistic antitumor activities.

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