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Long Y.,Chinese PLA General Hospital | Long Y.,Nankai University | Sun Q.,Chinese PLA General Hospital | Wu J.,Chinese PLA General Hospital | And 2 more authors.
Oncology Letters | Year: 2014

Immunotherapy may be an effective and potentially less toxic treatment for cancer in addition to the traditional therapies. The current study presents a case of advanced pancreatic cancer that was treated with cellbased immunotherapy using expanded activated allogeneic lymphocytes (EAAL*) in vitro with cluster of differentiation (CD)3(+) and CD8(+) cytotoxic T lymphocytes, and CD3() and CD56(+) natural killer cells as the major effector cells, together with chemotherapy and targeted agents. A 46yearold female was diagnosed at the Chinese PLA General Hospital (Beijing, China) with stage IV pancreatic cancer with multiple metastases in October 2012. After receiving one cycle of chemotherapy plus nimotuzumab (Nimo), the patient received 14 infusions of EAAL*, which was obtained from a related donor, combined with seven cycles of chemotherapy with gemcitabine plus oxaliplatin and targeted therapy with Nimo. The patient was followed up for eight months. One day prior to the cell infusion, targeted therapy was administered and 48 h following the cell infusion, chemotherapy was administered. Following this treatment, carbohydrate antigen 19-9 levels decreased from 4,136 U/ml to within the normal ranges, along with the significant regression of the lesions. Occasionally mild upset was observed following the EAAL* transfusion. For the entire combined modality, grade II hematological and gastrointestinal toxicities plus grade I liver function damage and skin rash were identified. The present study demonstrated that combining allogeneic cellbased immunotherapy with conventional therapies is effective and safe, even in patients with endstage pancreatic cancer. Therefore, this strategy is recommended for the treatment of similar cases. Source


Long Y.-Y.,Chinese PLA General Hospital | Long Y.-Y.,Nankai University | Wang Y.,Beijing ImmunoTech Applied Science Ltd | Huang Q.-R.,Beijing ImmunoTech Applied Science Ltd | And 2 more authors.
Experimental and Therapeutic Medicine | Year: 2014

NY-ESO-1 has been identified as one of the most immunogenic antigens; thus, is a highly attractive target for cancer immunotherapy. The present study analyzed the expression of serum antibodies (Abs) against NY-ESO-1 in patients with advanced colorectal cancer (CRC), with the aim of guiding the treatment of NY-ESO-1-based specific-immunotherapy for these patients. Furthermore, the present study was the first to evaluate the kinetic expression of anti-NY-ESO-1 Abs and investigate the possible influencing factors. A total of 239 serum samples from 155 pathologically confirmed patients with advanced CRC (stages III and IV) were collected. The presence of spontaneous Abs against NY-ESO-1 was analyzed using an enzyme-linked immunosorbent assay (ELISA). The results demonstrated that 24.5% (38/155) of the investigated patients were positive for NY-ESO-1-specific Abs. No statistically significant correlations were identified between the expression of anti-NY-ESO-1 Abs and clinicopathological parameters, including age and gender, location, grading, local infiltration, lymph node status, metastatic status and K-ras mutation status (P>0.05). In 59 patients, the kinetic expression of anti-NY-ESO-1 Abs was analyzed, of which 14 patients were initially positive and 45 patients were initially negative. Notably, 16/59 (27.1%) patients changed their expression status during the study period, and the initially positive patients were more likely to change compared with the initially negative patients (85.7 vs. 8.8%; P<0.001). Therefore, monitoring serum Abs against NY-ESO-1 by ELISA is an easy and feasible method. The high expression rate of NY-ESO-1-specific Abs in CRC patients indicates that measuring the levels of serum Abs against NY-ESO-1 may guide the treatment of NY-ESO-1-based specific immunotherapy for patients with advanced CRC. Source


Zhang G.-Q.,Chinese PLA General Hospital | Li F.,Chinese PLA General Hospital | Sun S.-J.,Chinese PLA General Hospital | Hu Y.,Chinese PLA General Hospital | And 4 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2015

Background: To investigate the clinical efficacy of expanded activated autologous lymphocytes (EAAL) in patients with small cell lung cancer (SCLC). Materials and Methods: A total of 32 SCLC patients were selected and randomly divided into EAAL treatment and control groups, 16 cases in each. EAAL were obtained by proliferation of peripheral blood mononuclear cells (PBMCs) of patients followed by phenotype determination. Clinical data of all patients were recorded. Patients of both groups were followed up and the overall survival (OS) were compared retrospectively. Results: After culture and proliferation in vitro, the percentages of CD3+, CD3+CD8+, CD45RO+, CD28+, CD29+, CD8+CD28+ and CD3+CD16+/CD56+ cells increased markedly (p<0.05). The OS of the EAAL treatment group was longer than that of control group, but the difference was not statistically significant (p=0.060, HR=0.487, 95%CI 0.228~1.037). 1- to 3-year survival rates in EAAL treatment group were longer than those in control group, but there was still no significant difference (p>0.05). COX multivariate regression analysis showed that the number of chemotherapy cycles and the application of EAAL immunotherapy were independent prognostic factors for SCLC patients. The OS in females and chemotherapy ≤6 cycles were obviously prolonged after EAAL immunotherapy. Conclusions: In vitro induction and proliferation of EAAL is easy and biologically safe. Generally, EAAL adoptive immunotherapy can evidently prolong the OS of SCLC patients. Source


Zhang G.-Q.,Chinese PLA General Hospital | Zhao H.,Chinese PLA General Hospital | Wu J.-Y.,Chinese PLA General Hospital | Li J.-Y.,Chinese PLA General Hospital | And 7 more authors.
World Journal of Gastroenterology | Year: 2015

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. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved. Source

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