Phase I clinical trial of adoptive transfer of expanded natural killer cells in combination with IgG1 antibody in patients with gastric or colorectal cancer. Issue 12 (14th February 2018)

• Record Type: Journal Article
• Authors: Ishikawa, Takeshi; Okayama, Tetsuya; Sakamoto, Naoyuki; Ideno, Mitsuko; Oka, Kaname; Enoki, Tatsuji; Mineno, Junichi; Yoshida, Naohisa; Katada, Kazuhiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Handa, Osamu; Takagi, Tomohisa; Konishi, Hideyuki; Kokura, Satoshi; Uno, Kazuko; Naito, Yuji; Itoh, Yoshito
• Is Part Of: International journal of cancer. Volume 142:Issue 12(2018)
• Page Start: 2599
• Page End: 2609
• Publication Date: 2018-02-14
• Subjects: adoptive NK therapy -- antibody‐dependent cellular cytotoxicity (ADCC) -- trastuzumab -- cetuximab; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31285
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Natural killer (NK) cells exhibit strong cytotoxic activity against tumor cells without prior sensitization, and have the potential to exert antibody‐dependent cellular cytotoxicity (ADCC). In this clinical trial, we examined the safety and efficacy of the use of NK cells, generated using a novel expansion system, in combination with IgG1 antibodies for the treatment of advanced gastric or colorectal cancers. Treatment consisted of trastuzumab‐ or cetuximab‐based chemotherapy, plus adoptive NK cell therapy. For administration of expanded NK cells, dose escalation with a sequential 3 + 3 design was performed in three steps, at doses of 0.5 × 10 9, 1.0 × 10 9, and 2.0 × 10 9 cells/injection ( N = 9). After 3 days of IgG1 antibody administration, patients were infused with expanded NK cells three times at triweekly intervals. NK cell populations expanded with our system were confirmed as being enriched in NK cells (median 92.9%) with high expression of NKG2D (97.6%) and CD16 (69.6%). The combination therapy was very well tolerated with no severe adverse events. Among six evaluable patients, four presented stable disease (SD) and two presented progressive disease. Of the four SD patients, three showed an overall decrease in tumor size after combination therapy. Immune monitoring suggested that combination therapy enhanced whole blood IFN‐γ production and reduced peripheral regulatory T cells (Tregs). In conclusion, this phase I trial provides evidence of good tolerability, induction of Th1 immune responses, and preliminary anti‐tumor activity for this combination therapy, in patients with advanced gastric and colorectal cancer that have received previous therapy. Abstract : What's new? Cell‐mediated and antibody‐based approaches have each emerged as promising cancer treatments. Here the authors combined both approaches and performed a first clinical trial of adoptive therapy with natural killer cells together with monoclonal antibodies trastuzumab or cetuximab. The treatment was well tolerated and three out of six patients with advanced gastric or colorectal cancer showed a decrease in tumor size. The results support the concept that antibody‐dependent cellular cytotoxicity might be enhanced with combination treatment, yielding favorable responses not observed with monotherapies.