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Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer.

ABSTRACT: Renal cell carcinoma (RCC) is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. Yet Active immunization using genetically modified dendritic cells holds promise for the adjuvant treatment of malignancies to eradicate or control residual disease. Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD8+ T cells with diverse TCR specificities, possessing non-MHC-restricted cytolytic activities against tumor cells. Clinical studies have confirmed benefit and safety of CIK cell-based therapy for patients with malignancies. This clinical trial was conducted to evaluate efficacy and safety of genetically modified dendritic cells in combination with Cytokine-Induced Killer Cell (gmDCs-CIK) treatment of patients with RCC.28 patients with advanced renal cancer were admitted to Affiliated Hospital of Academy of Military Medical Sciences from December 2010 to March 2012 and treated by gmDCs-CIK. Clinical efficacy and safety between pre- and post-treatment were compared.This analysis showed an objective response rate (ORR) of 39% and a disease control rate (DCR) of as 75%. There is no significant relationship between clinical efficacy and whether metastasis occurred or not (P?>?0.05). There is no significant relationship between ORR and cycles of treatment (P?>?0.05), but DCR was significantly related with cycles of treatment (P?

SUBMITTER: Wang D

PROVIDER: S-EPMC3997215 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer.

Wang Danhong D Zhang Bin B Gao Haiyan H Ding Guoliang G Wu Qiong Q Zhang Jinchao J Liao Li L Chen Hu H

BMC cancer 20140410

<h4>Background</h4>Renal cell carcinoma (RCC) is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. Yet Active immunization using genetically modified dendritic cells holds promise for the adjuvant treatment of malignancies to eradicate or control residual disease. Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD8+ T cells with diverse TCR specificities, possessing non-MHC-restricted cytolytic activities against tumor cells. Cli ...[more]

PMID: 24720900

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Project description:BackgroundRadical/cytoreductive nephrectomy or nephron-sparing surgery may be thought to be not safe or unfeasible in some renal cell carcinoma (RCC) patients in which tumor is locally advanced or highly complicated. Neoadjuvant therapy may reduce the volume of the tumor, thus facilitates surgery. The aim the study is to evaluate the efficacy and safety of neoadjuvant combination of pazopanib or axitinib and PD-1-activated dendritic cell-cytokine-induced killer (PD-1/DC-CIK) cell immunotherapy in those patients.MethodsData from 16 RCC patients who received neoadjuvant pazopanib (Group P, n=9) or axitinib (Group A, n=7) plus PD-1/DC-CIK cells immunotherapy were reviewed retrospectively. A total of 9 participants that were potential candidates for radical/cytoreductive nephrectomy (RN/CN) had locally advanced tumor and 5 participants with partial nephrectomy (PN) absolute indications had highly complicated tumors. The efficacy outcomes were based on volume changes of the primary tumor, lymph nodes, and tumor thrombus in 13 participants with complete computed tomography (CT) imaging. The treatment-related toxicities and surgical complications were also reported.ResultsWith a median of 2.1 months treatment, the overall volume of the tumors decreased by a median of 42.30% [interquartile range (IQR): 19.37-66.78%]. Specifically, the median reduction of tumor volume was 88.77 and 15.50 cm3 in group P and group A, respectively (P=0.014). However, participants in Group P were more likely to experience grade 3 or 4 treatment-related adverse events (AEs) than those in Group A (44.4% vs. 0). Finally, all participants were candidates for appropriate surgery after neoadjuvant therapy (as assessed by the surgeon), and 10 participants accepted surgery, including 5 PN, 4 RN/CN, and 1 lymph node dissection. A solitary participant had Clavien grade IV acute renal failure required dialysis and another had grade II lymphatic leakage.ConclusionsNeoadjuvant combination of pazopanib or axitinib and PD-1/DC-CIK cells immunotherapy was well-tolerated and could effectively reduce the volume of tumors in locally advanced or highly complicated RCC patients.

Dataset Information

Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer.

Publications

Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer.

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