Open AccessNatural killer cell engineering for cellular therapy of cancer
Author(s) -
Shook D. R.,
Campana D.
Publication year - 2011
Publication title -
tissue antigens
Language(s) - English
Resource type - Journals
eISSN - 1399-0039
pISSN - 0001-2815
DOI - 10.1111/j.1399-0039.2011.01796.x
Subject(s) - chimeric antigen receptor , cancer immunotherapy , immunotherapy , biology , cell , effector , lymphokine activated killer cell , cancer research , natural killer cell , k562 cells , leukemia , microbiology and biotechnology , immunology , cytotoxicity , t cell , interleukin 21 , immune system , in vitro , genetics
Natural killer (NK) cells can kill transformed cells and represent a promising tool for the treatment of cancer. Their function is governed by a balance of stimulatory and inhibitory signals triggered by surface receptors. Advances in NK cell therapy require the development of dependable methods for obtaining an adequate number of effector cells; additional activation or genetic modification may further increase their anticancer capacity. A method for NK cell expansion used in our laboratory relies on a genetically modified form of the K562 myeloid leukemia cell line, engineered to express a membrane‐bound form of interleukin‐15 and the ligand for the costimulatory molecule 4‐1BB (CD137). Expanded NK cells can be transduced with genes encoding chimeric antigen receptors that stimulate tumor cell‐specific cytotoxicity. These methods for NK cell expansion and genetic modification have been adapted to large‐scale, clinical‐grade, Current Good Manufacturing Practice conditions and support two active clinical trials. Summarized are current efforts for NK cell immunotherapy for cancer and future perspectives.