Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer

• DOI: 10.1186/s12967-015-0632-8
• Publication Date: 2015-08-24T16:49:20Z
• Authors: Naoyuki Sakamoto; Takeshi Ishikawa; Satoshi Kokura; Tetsuya Okayama; Kaname Oka; Mitsuko Ideno; Fumiyo Sakai; Akiko Kato; Masashige Tanabe; Tatsuji Enoki; Junichi Mineno; Yuji Naito; Yoshito Itoh; Toshikazu Yoshikawa
• Keywords: Medicine(all); Male; 0303 health sciences; Biochemistry, Genetics and Molecular Biology(all); Research; Middle Aged; Immunophenotyping; 3. Good health; Killer Cells, Natural; 03 medical and health sciences; Humans; Female; Immunotherapy; Aged; Gastrointestinal Neoplasms

NK cells can destroy tumor without prior sensitization or immunization. Tumors often lose expression of MHC molecules and/or antigens. However, lyse in a non-MHC-restricted manner and independent the tumor-associated are therefore considered ideal for adoptive cancer immunotherapy; however difficulty obtaining large numbers fully functional that safe to administer deters its clinical use. This phase I trial seeks address this obstacle by first developing novel system expands highly activated grade cells, second, determining if these mono-treatment so they be combined with other reagents next round trials. Patients unresectable, locally advanced metastatic digestive who did not succeed standard therapy were enrolled. expanded ex vivo stimulating PBMCs OK432, IL-2, modified FN-CH296 induced T cells. administered autologous natural killer cell three times weekly via intravenous infusions dose-escalating (dose 0.5 × 109, 1.0 2.0 109 cells/injection, patients/one cohort). Total population had median expansion 586-fold (range 95–1102), significantly pure (90.96 %) population. Consequently, approximately 4720-fold 1372–14,116) being lytic vitro strongly expressing markers such as NKG2D CD16. was very well tolerated no severe adverse events. Although responses observed, cytotoxicity peripheral blood elevated twofolds up 4 weeks post last transfer. We successfully generated from small quantities purification also determined monotherapy suitable trials where their efficacy will tested reagents. Trial Registration: UMIN UMIN000007527