In vivo trafficking and survival of cytokine-induced killer cells resulting in minimal GVHD with retention of antitumor activity

Nishimura, Ryosei; Baker, Jeanette; Beilhack, Andreas; Zeiser, Robert; Olson, Janelle A.; Sega, Emanuela I.; Karimi, Mobin; Negrin, Robert S.

doi:10.1182/blood-2007-06-092817

Cited by 166 publications

(147 citation statements)

References 35 publications

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“…The lower incidence of GHVD of allogeneic CIK cells have been convincingly shown in mouse models, 28 and was postulated to be due to less trafficking of CIK cells to GVHD sites. 29 This was also consistent with an earlier report on activated donor lymphocytes expanded with CD3/CD28 coated beads, where GVHD was observed in 7 out of 18 patients. 17 In two Phase I studies using allogeneic CIK for relapsed patients, acute GVHD occurred in 4 out of 11 patients 30 and 1 out of 10 patients, 16 respectively.…”

Section: Discussionsupporting

confidence: 82%

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

Niam

et al. 2011

Bone Marrow Transplant

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We performed a Phase I/II clinical trial to study the feasibility, toxicity and efficacy of allogeneic cytokineinduced killer (CIK) cell expansion, and treatment for patients with haematological malignancies who relapsed after allogeneic haemopoietic SCT (allo-HSCT). Allogeneic CIK cells were successfully generated for a total of 24 patients, including those from patients' own leukapheresis products in 5 patients who had no access to further donor cells. The median CD3 þ T-cell expansion was 9.33 (1.3-38.97) fold, and CD3 þ CD56 þ natural killer (NK)-like T-cell expansion was 27.77 (2.59-438.93) fold. A total of 55 infusions were done for 16 patients who had either failed or progressed after initial response to various individualized chemotherapy regimens and donor lymphocyte infusion (DLI), at doses ranging from 10 to 200 million CD3 þ cells/kg. Response attributable to CIK cell infusion was observed in five patients. These included two with ALL, two with Hodgkin's disease (HD) and one with AML, and two of whom had a response sustained for more than 2 years. Acute GVHD occurred in three and was easily treatable. This study provides some evidence suggestive of the efficacy of allogeneic CIK cells even after failure of DLI in some cases.

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Section: Discussionsupporting

confidence: 82%

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

Niam

et al. 2011

Bone Marrow Transplant

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“…51 (2) Natural killer (NK) cells, which are inhibited by recognition of class I alleles on target cells through the killer Ig-like receptors, downregulate APC activation of T cells perhaps by directly killing APCs. [52][53][54] (3) Host NKT cells can negatively regulate APC interactions with donor T cells in an IL-4-and Th2-dependent manner. 55,56 In contrast, donor NKT cells activate this response.…”

Section: Sensors Of Gvhdmentioning

confidence: 99%

New perspectives on the biology of acute GVHD

Paczesny

Hanauer

Sun

et al. 2009

Bone Marrow Transplant

151

126

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The use of allogeneic hematopoietic cell transplantation (HCT) has increased as new techniques have been developed for transplantation in patients who previously would not have been considered HCT candidates. However, its efficacy continued to be limited by the development of frequent and severe acute GVHD. The complex and intricate pathophysiology of acute GVHD is a consequence of interactions between the donor and host innate and adaptive immune responses. Multiple inflammatory molecules and cell types are implicated in the development of GVHD that can be categorized as:(1) triggers that initiate GVHD by therapy-induced tissue damage and the antigen disparities between host and graft tissue; (2) sensors that detect the triggers, that is, process and present alloantigens; (3) mediators such as T-cell subsets (naive, memory, regulatory, Th17 and natural killer T cells) and (4) the effectors and amplifiers that cause damage of the target organs. These multiple inflammatory molecules and cell types that are implicated in the development of GVHD have been described with models that use stepwise cascades. Herein, we provide a novel perspective on the immunobiology of acute GVHD and briefly discuss some of the outstanding questions and limitations of the model systems.

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“…The use of immunosuppressive drugs, such as CsA and FK506, prevented the degranulation of CIK cells that is induced by CD3-TCR stimulation; however, the drugs were unable to block the cytotoxicity that was triggered by the interaction with tumor targets. In addition, the degranulation induced by target cells was unaffected by CsA and FK506 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)21). Therefore, the use of immunosuppressive drugs may not affect the efficacy of CIK.…”

Section: Discussionmentioning

confidence: 91%

“…Autologous activated immune cells, including cytokine-induced killer (CIK) cells, are a unique population of cytotoxic T lymphocytes that express natural killer and T-cell markers, and may be generated from peripheral blood mononuclear cells treated with interferon (IFN)-γ, anti-cluster of differentiation (CD)3 monoclonal antibody, and interleukin (IL)-2. These CIK cells have demonstrated increased proliferative and cytotoxic activities against autologous and allogeneic malignant cells (10,11). Previous studies also report that adoptive immunotherapy using autologous CIK cells may decrease tumor recurrence and metastasis in postsurgical and advanced liver cancer patients (12,13).…”

Section: Introductionmentioning

confidence: 94%

Cytokine-induced killer cell therapy for the treatment of primary hepatocellular carcinoma subsequent to liver transplantation: A case report

Fang

Liu

et al. 2016

Oncology Letters

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Abstract. Liver cancer, of which the most common form is hepatocellular carcinoma (HCC), is one of the most lethal cancers worldwide. Immunotherapy based on the direct attack of tumor cells and the stimulation of an antitumor immune response may represent a novel strategy to control HCC recurrence and metastasis. The present study reports the case of a patient with HCC, and describes the safety and feasibility of successful administration with a mass of autologous activated T cells on numerous occasions subsequent to liver transplantation (LT), in order to kill the residual tumor cells and stimulate the immune system. A large number of infused activated T cells may pose a potential risk to the allograft. However, no acute or delayed adverse effects of cytokine-induced killer cell (CIK) therapy, or other symptoms of secondary acute host-versus-graft disease (HVGD), were observed. These observations demonstrate the relatively low toxicity of CIK infusion to a patient that has undergone LT, and more importantly, they demonstrate the feasibility of this immunotherapy for the patient, following successful LT.

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In vivo trafficking and survival of cytokine-induced killer cells resulting in minimal GVHD with retention of antitumor activity

Cited by 166 publications

References 35 publications

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

New perspectives on the biology of acute GVHD

Cytokine-induced killer cell therapy for the treatment of primary hepatocellular carcinoma subsequent to liver transplantation: A case report

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