Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2015; 21(9): 2777-2785
Published online Mar 7, 2015. doi: 10.3748/wjg.v21.i9.2777
Prolonged overall survival in gastric cancer patients after adoptive immunotherapy
Guo-Qing Zhang, Hong Zhao, Jian-Yu Wu, Jin-Yu Li, Xiang Yan, Gang Wang, Liang-Liang Wu, Xiao-Gang Zhang, Yi Shao, Yu Wang, Shun-Chang Jiao
Guo-Qing Zhang, Hong Zhao, Jian-Yu Wu, Jin-Yu Li, Xiang Yan, Shun-Chang Jiao, Department of Clinical Oncology, Chinese PLA General Hospital, Beijing 100853, China
Gang Wang, Liang-Liang Wu, Laboratory of Tumor Research Center, Chinese PLA General Hospital, Beijing 100853, China
Xiao-Gang Zhang, Yi Shao, Yu Wang, Beijing Immunotech Applied Science Limited, Beijing 101111, China
Author contributions: Zhang GQ and Zhao H contributed equally to this work; Zhang GQ contributed to study design, writing and revision of the manuscript; Zhao H contributed to the patient enrollment and data analysis; Jiao SC contributed to study conception and design, critical revision of the manuscript, and financial support prior to publication; Wu JY, Li JY and Yan X contributed to patient enrollment; Wang G, Wu LL and Zhang XG analyzed the lymphocyte subtypes; Shao Y and Wang Y prepared EAAL samples; and all authors have read and approved the final manuscript.
Supported by National Science and Technology Infrastructure Program of China, No. 2009BAI86B05.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shun-Chang Jiao, MD, PhD, Department of Clinical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. medscijsc@126.com
Telephone: +86-10-66937261 Fax: +86-10-68238924
Received: June 23, 2014
Peer-review started: June 24, 2014
First decision: August 6, 2014
Revised: September 4, 2014
Accepted: November 18, 2014
Article in press: November 19, 2014
Published online: March 7, 2015
Processing time: 259 Days and 0.9 Hours
Abstract

AIM: To assess the efficacy of immunotherapy with expanded activated autologous lymphocytes (EAALs) in gastric cancer.

METHODS: An observational study was designed to retrospectively analyze the clinical data of 84 gastric cancer patients, of whom 42 were treated by EAAL immunotherapy plus conventional treatment and another 42 only received conventional treatment (control group). EAALs were obtained by proliferation of peripheral blood mononuclear cells from patients followed by phenotype determination. Clinical data including age, gender, clinical stage, chemotherapeutic regimens, hospitalization, surgical, radiotherapy, and survival data were collected along with EAAL therapy details and side effects. Patients were followed and the relationship between treatment and overall survival (OS) data obtained for the immunotherapy and control groups were compared retrospectively. The safety of EAAL immunotherapy was also evaluated.

RESULTS: After in vitro culture and proliferation, the percentages of CD3+, CD3+CD8+, CD8+CD27+, CD8+CD28+, and CD3+CD16+/CD56+ cells increased remarkably (P < 0.05), while the percentages of CD3+CD4+, CD4+CD25+, and CD3-CD16+/CD56+ (natural killer cells) were overtly decreased (P < 0.05); no significant change was observed in CD4+CD25+CD127- cells (P = 0.448). Interestingly, OS in the immunotherapy group was significantly higher than that in the control group, with 27.0 and 13.9 mo obtained for the two groups, respectively (P = 0.028, HR = 0.573, 95%CI: 0.347-0.945). These findings indicated a 42.7% decrease in the risk of death. In addition, we found that clinical stage and application of EAAL immunotherapy were independent prognostic factors for gastric cancer patients. Indeed, the OS in stage IIIc and IV patients that had received surgery was prolonged after EAAL immunotherapy (P < 0.05). Importantly, in vitro induction and proliferation of EAAL were easy and biologically safe.

CONCLUSION: Overall, EAAL adoptive immunotherapy might prolong the OS in gastric cancer patients.

Keywords: Adoptive immunotherapy, Gastric cancer, Expanded activated autologous lymphocytes, Lymphocytes, Observational study

Core tip: We undertook a retrospective analysis of patients with gastric cancer to perform an observational study on whether expanded activated autologous lymphocytes (EAALs) improved treatment outcomes. The results provide the first evidence for EAALs being an effective treatment regimen in gastric cancer. The therapy was straightforward and showed good safety, and overall survival may be improved with EAAL treatment in gastric cancer patients.