演題抄録

ポスター

開催概要
開催回
第56回・2018年・横浜
 

切除不能進行胃癌・大腸癌に対する高純度NK細胞+IgG1抗体薬併用療法の第1相臨床試験

演題番号 : P17-2

[筆頭演者]
演者)石川 剛:1 
[共同演者]
岡山 哲也:1、坂元 直行:1、出野 美津子:2、岡 要:1、榎 竜嗣:2、峰野 純一:2、古倉 聡:1、内藤 裕二:1,2、伊藤 義人:1

1:京都府立医科大学・消化器内科、2:タカラバイオ株式会社・CDMセンター

 

Background NK cells kill tumor cells by natural cytotoxicity, and can be activated upon binding of antibodies to Fc-receptors on their surface mediating antibody-dependent cellular cytotoxicity (ADCC). So, adoptive NK cell therapy would be expected to enhance the efficacy and overcome the resistance of IgG1 antibodies by augmenting ADCC. Thus, we evaluated the safety and efficacy of NK cell therapy combined with IgG1 antibodies.
Patients and Methods Patients with un-resectable, metastatic gastric or colorectal cancer, who had been administered IgG1 antibody or were scheduled for administration, were enrolled. (i.e. trastuzumab for HER2 positive gastric cancer or cetuximab for RAS-wild colorectal cancer). NK cells were expanded from PBMCs with the same method in previous clinical trial (J Transl Med (2015) 13:277), briefly ex vivo by stimulating PBMCs with OK432, IL-2, and modified FN-CH296-induced T cells. Expanded NK cells were intravenously injected 3 days after IgG1 antibody administration in a dose-escalating manner (dose 0.5 × 109, 1.0 × 109, 2.0 × 109 cells/injection, three patients/one cohort), every 3 weeks for 3 cycles. We evaluated the safety, efficacy, and immunological response of the combination therapy.
Results Nine eligible patients were enrolled. Expanded NK cell populations were confirmed as being enriched in NK cells (median 92.9%) with high expression of NKG2D(97.6%) and CD16(69.6%). This combination therapy was well tolerated with no severe adverse events. Among six evaluable patients, 4 presented SD, 2 presented PD. Of the four SD patients, 3 showed an overall decrease in tumor size. Whole blood IFN-γ production level was increased after the combination therapy.
Conclusion This is the first clinical trial of adoptive NK cell therapy combined with IgG1 antibodies.Our trial provides evidence of good tolerability, induction of Th1 immune response, and preliminary anti-tumor activity for the combination of adoptive NK cell therapy and IgG1 antibodies.

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臓器別:その他

手法別:免疫療法

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