Efficacy and safety of cord blood–derived cytokine-induced killer cells in treatment of patients with malignancies

Zhang, Zhen; Wang, Liping; Luo, Zhenzhen; Zhao, Xuan; Huang, Jianmin; Li, Hong; Yang, Shuman; Zhao, Xin; Zhang, Lei; Li, Liuxia; Wang, Feng; Huang, Lan; Zhang, Yi

doi:10.1016/j.jcyt.2015.04.002

Cited by 22 publications

(20 citation statements)

References 39 publications

(35 reference statements)

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“…109,129 ACT was performed with TILs 28,116,117,122 including TILs obtained from tumor-invaded bone marrow 113 or sentinel lymph nodes, 55 CTLs recognizing proteins from tumor-associated viruses 109,129 or lymphocytes activated ex vivo by cytokines including interferon gamma (IFN-g) and IL-2. 53,107,118,120,121,123,128 In some cases, adoptively transferred T cells were engineered to express CAR-specific TAAs including carcinoembryonic antigen (CEA), 125 erb-b2 receptor tyrosine kinase 2 (ERBB2, best known as HER2), 126 interleukin 13 receptor subunit alpha 2 (IL13RA2), 43,127 CD19, 42,106,111,112 TNF receptor superfamily member 17 (TNFRSF17, best known as BCMA), 114,115 or TCR recognizing TAAs like MAGE family member A4 (MAGEA4). 119 The high heterogeneity in the types of cancer treated with ACT-based immunotherapy in these aforementioned studies and in the approaches chosen for delivering selective populations of cytotoxic immune cells complicated remarkably the evaluation of therapeutic efficacy.…”

Section: Literature Updatementioning

confidence: 99%

“…The first one was the number of complete responses (CRs) or partial responses (PRs) as per Response Evaluation Criteria in Solid Tumors (RECIST). 130 Among the 8 papers in which an objective response was investigated, 28,53,107,116,117,119,124,126 5 documented both CRs and PRs, for a total of 12 CRs and 18 PRs over 78 patients, 28,53,107,116,117 whereas no objective response was observed in the 3 remaining studies (including 41 additional patients). 119,124,126 Objective CRs and PRs were documented in 3 studies enrolling metastatic melanoma patients treated with TILs expanded and activated ex vivo, 28,116,117 and in 2 studies in which B-cell lymphoma patients received CIK cells obtained from peripheral blood cells, 107 or hepatocellular and esophageal carcinoma patients were treated with CIK cells obtained from the cord blood.…”

Section: Literature Updatementioning

confidence: 99%

“…50,51 Because TILs cannot be employed for ACT-based immunotherapy in many cases, novel strategies have been developed and tested. Thus, ACT can also rely on lymphocytes from the peripheral blood (in both autologous and heterologous settings), and occasionally from the cord blood (in heterologous settings only) 52,53 or the sentinel lymph node (in autologous settings only). 54,55 Once isolated, lymphocytes may be genetically modified to express a selected T cell receptor (TCR) or a chimeric antigen receptor (CAR), both of them allowing CTLs to target specific TAAs.…”

Section: Introductionmentioning

confidence: 99%

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Trial Watch: Adoptively transferred cells for anticancer immunotherapy

et al. 2017

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Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated , and administered to lymphodepleted patients. ACT may be optionally associated with chemo- and/or immunotherapeutics, with the overall aim of enhancing the proliferation, persistence and functionality of infused cells, as well as to ensure their evolution in an immunological permissive local and systemic microenvironment. In addition, isolated lymphocytes can be genetically engineered to endow them with the ability to target a specific tumor-associated antigen (TAA), to increase their lifespan, and/or to reduce their potential toxicity. The infusion of chimeric antigen receptor (CAR)-expressing cytotoxic T lymphocytes redirected against CD19 has shown promising clinical efficacy in patients with B-cell malignancies. Accordingly, the US Food and Drug Administration (FDA) has recently granted 'breakthrough therapy' designation to a CAR-based T-cell therapy (CTL019) for patients with B-cell malignancies. Considerable efforts are now being devoted to the development of efficient ACT-based immunotherapies for non-hematological neoplasms. In this Trial Watch, we summarize recent clinical advances on the use of ACT for oncological indications.

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Section: Literature Updatementioning

confidence: 99%

Section: Literature Updatementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Trial Watch: Adoptively transferred cells for anticancer immunotherapy

et al. 2017

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“…The CB-CIK cells displayed relatively lower expression of HLA, indicating a weaker immunogenicity and lower risk of GVHD (42). Many clinical trials proved that CB-CIK cells were effective and safe to patients with malignancies (43, 44). All these suggest that CIK is a safe immune therapy with lower risk of GVHD.…”

Section: Ex Vivo Expansion and Alloreactivity Of Cik Cellsmentioning

confidence: 99%

Cytokine-Induced Killer Cells As Pharmacological Tools for Cancer Immunotherapy

et al. 2017

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Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3+CD56+ natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor. Furthermore, we briefly sum up the clinical trials on CIK cells and compare the effect of clinical CIK therapy with other immunotherapies. Finally, further research is needed to clarify the pharmacological mechanism of CIK and provide evidence to formulate uniform culturing criteria for CIK expansion.

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“…CIK cells are a heterogeneous subset of exvivo expanded T lymphocytes [10]- [12]. They present a mixed T-NK phenotype and are endowed with the MHC-unrestricted antitumor activity, which means it can kill cancer cells without attacking the normal cells [13,14]. Although CIK cells have the ability to kill cancer cells, the curative effect is not obvious in a short time.…”

Section: Introductionmentioning

confidence: 99%

Human CIK Cells Loaded with Gold Nanoprisms as Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immuno-Photothermal Combined Therapy

Zhang¹,

Xia²,

Yang³

et al. 2016

Nano BioMed ENG

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How to enhance the therapeutic efficacy of human cytokine induced killers cell (CIK) has become a great challenge. Herein, we report for the first time that human CIK cells loaded with gold nanoprisms were successfully used for targeted photoacoustic imaging, enhanced immunotherapy and photothermal therapy of gastric cancer in vivo. Gold nanoprisms were synthesized and modified with PEG; human CIK cells were prepared and incubated with PEGylated gold nanoprisms (Au GNPrs), and then the effects of human CIK cells labeled with Au NPrs on gastric cancer MGC 803 cells were evaluated and further used for targeted photoacoustic imaging, immunotherapy and photothermal therapy of gastric cancer in vivo in mice models. Results showed that PEGylated Au NPrs could be uptaken high-efficiently by human CIK cells, resultant human CIK cells labeled with AuNPrs could inhibit the growth of gastric cancer MGC 803 cells actively by induced apoptosis and G1 phase arrest, and actively target and accumulate the tumor sites in gastric cancer-bearing nude mice. Enhanced synergistic therapeutic efficacy was demonstrated with the maximal inhibition of tumor through a combination of CIK cells-based immunotherapy for three days and then a continuous gold nanoprisms-based photothermal therapy. In conclusion, human CIK cells labeled with PEGylated Au NPrs can target gastric cancer cells in vivo, enhance immunotherapy and photothermal therapy efficacy, and have a great potential in applications such as targeted imaging, immunotherapy and photothermal therapy of gastric cancer in the near future.

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Efficacy and safety of cord blood–derived cytokine-induced killer cells in treatment of patients with malignancies

Cited by 22 publications

References 39 publications

Trial Watch: Adoptively transferred cells for anticancer immunotherapy

Trial Watch: Adoptively transferred cells for anticancer immunotherapy

Cytokine-Induced Killer Cells As Pharmacological Tools for Cancer Immunotherapy

Human CIK Cells Loaded with Gold Nanoprisms as Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immuno-Photothermal Combined Therapy

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