Interleukin-15-activated cytokine-induced killer cells may sustain remission in leukemia patients after allogeneic stem cell transplantation: feasibility, safety and first insights on efficacy

Rettinger, Eva; Huenecke, Sabine; Bönig, Halvard; Merker, Matthias; Jarisch, Andrea; Soerensen, Jan; Willasch, André; Bug, Gesine; Schulz, Ansgar; Klingebiel, Thomas; Bader, Peter

doi:10.3324/haematol.2015.138016

Cited by 36 publications

(52 citation statements)

References 15 publications

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“…3 These cells have been demonstrated to be safe with limited toxicity, but they may induce GVHD and, to date, only limited efficacy has been reported. 3,5,17,25,26 Their use more than likely will be best prior to overt relapse or in combination with other therapies. 5…”

Section: Cytokine-induced Killer Cellsmentioning

confidence: 98%

Cells to prevent/treat relapse following allogeneic stem cell transplantation

Dietz

Wayne²

2017

Hematology

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Relapse of cancer remains one of the primary causes of treatment failure and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). A multitude of approaches have been used in the management of posttransplant relapse. This review focuses on recent data with cellular therapies designed to treat or prevent posttransplant relapse of hematologic malignancies, although many of these therapeutic approaches also have applications to solid tumors and in the nontransplant setting. Currently available cell therapies include second transplant, natural killer cells, monocytederived dendritic cell vaccines, and lymphocytes via donor lymphocyte infusion, antigen-primed cytotoxic T lymphocytes, cytokine-induced killer cells, marrow-infiltrating lymphocytes, and chimeric antigen receptor T cells. These treatment options offer the prospect for improved relapse-free survival after HSCT. Learning Objectives• Understand the biologic basis, potential advantages, and risks of specific cell-based cancer therapies • Gain knowledge about recent results of cellular therapies used in the prevention and treatment of relapse after allogeneic HSCT Conflict-of-interest disclosure: A.S.W. has received research funding from MedImmune, Kite Pharma, and Spectrum Pharmaceuticals and has served on an advisory committee for Servier. He also is the co-inventor of investigational products with patents assigned to the National Institutes of Health. A.C.D. declares no competing financial interests.Off-label drug use: None disclosed.

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Section: Cytokine-induced Killer Cellsmentioning

confidence: 98%

Cells to prevent/treat relapse following allogeneic stem cell transplantation

Dietz

Wayne²

2017

Hematology

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“…Nevertheless, the transferred T cells may also lead to graft‐ versus ‐host‐disease (GvHD), which is a major cause of transplant‐related deaths. CIK cells have been proposed as an alternative to T cells for DLI as they show a reduced risk of causing GvHD . CIK cells are heterogeneous effector cells including T cells (CD3 + CD56 − ), natural killer (NK) cells (CD3 − CD56 + ) and natural killer T (T‐NK) cells (CD3 + CD56 + ) that exhibit non‐MHC‐restricted cytotoxicity and are expanded ex vivo from peripheral blood mononuclear cells (PBMCs) in the presence of interferon (IFN)‐γ, anti‐CD3 antibody and interleukin‐2 (IL‐2) …”

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confidence: 99%

“…Addition of IL‐15 to the expansion culture has resulted in enhanced cytotoxicity of CIK cells, and cells generated in this fashion are currently being tested in a clinical setting . Nevertheless, while CIK cells have shown potent activity against various other cancer types, cytotoxicity against B‐ALL has been less pronounced .…”

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confidence: 99%

Chimeric antigen receptor‐engineered cytokine‐induced killer cells overcome treatment resistance of pre‐B‐cell acute lymphoblastic leukemia and enhance survival

Oelsner

Wagner

Friede

et al. 2016

Intl Journal of Cancer

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Pre-emptive cancer immunotherapy by donor lymphocyte infusion (DLI) using cytokine-induced killer (CIK) cells may be beneficial to prevent relapse with a reduced risk of causing graft-versus-host-disease. CIK cells are a heterogeneous effector cell population including T cells (CD3(+) CD56(-) ), natural killer (NK) cells (CD3(-) CD56(+) ) and natural killer T (T-NK) cells (CD3(+) CD56(+) ) that exhibit non-major histocompatibility complex (MHC)-restricted cytotoxicity and are generated by ex vivo expansion of peripheral blood mononuclear cells in the presence of interferon (IFN)-γ, anti-CD3 antibody, interleukin-2 (IL-2) and interleukin-15 (IL-15). To facilitate selective target-cell recognition and enhance specific cytotoxicity against B-cell acute lymphoblastic leukemia (B-ALL), we transduced CIK cells with a lentiviral vector encoding a chimeric antigen receptor (CAR) that carries a composite CD28-CD3ζ domain for signaling and a CD19-specific scFv antibody fragment for cell binding (CAR 63.28.z). In vitro analysis revealed high and specific cell killing activity of CD19-targeted CIK/63.28.z cells against otherwise CIK-resistant cancer cell lines and primary B-ALL blasts, which was dependent on CD19 expression and CAR signaling. In a xenograft model in immunodeficient mice, treatment with CIK/63.28.z cells in contrast to therapy with unmodified CIK cells resulted in complete and durable molecular remissions of established primary pre-B-ALL. Our results demonstrate potent antileukemic activity of CAR-engineered CIK cells in vitro and in vivo, and suggest this strategy as a promising approach for adoptive immunotherapy of refractory pre-B-ALL.

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“…Specific studies highlighting the clinical application of CIK infusion for AML include a report by Wang et al describing a patient with RR-AML who experienced a dramatic reduction in leukemic burden after four CIK infusions given over 4 months [44]. A more recent study evaluated the safety and feasibility of IL-15-activated CIK cells as a means of preventing relapse in high-risk leukemia [45]. Four patients with detectable molecular relapse received between two and nine cycles of CIK infusions from either matched sibling or unrelated donors.…”

Section: Cytokine-induced Killer Cellsmentioning

confidence: 99%

Advances in Immunotherapy for Acute Myeloid Leukemia

2018

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Evasion of the host immune system is a key mechanism to promote malignant progression. Therapeutically targeting immune pathways has radically changed the treatment paradigm for solid and lymphoid tumors but has yet to be approved for myeloid malignancies. Here, we summarize the most recent advances in immunotherapy for acute myeloid leukemia. Topics reviewed here include adoptive cellular approaches (chimeric antigen receptor-T cells, natural killer and other immune cells), checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4 and TIM-3) and vaccines (WT-1, HLA-A2 and hTERT). Emphasis is placed on agents with clear evidence of tumor-specific immune responses and/or clinical activity in early-phase trials. Despite concerns regarding heterogeneous antigen expression and cytokine release syndrome, immunotherapy remains a highly promising strategy for acute myeloid leukemia, particularly transplant-ineligible patients and minimal residual disease states.

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Interleukin-15-activated cytokine-induced killer cells may sustain remission in leukemia patients after allogeneic stem cell transplantation: feasibility, safety and first insights on efficacy

Cited by 36 publications

References 15 publications

Cells to prevent/treat relapse following allogeneic stem cell transplantation

Cells to prevent/treat relapse following allogeneic stem cell transplantation

Chimeric antigen receptor‐engineered cytokine‐induced killer cells overcome treatment resistance of pre‐B‐cell acute lymphoblastic leukemia and enhance survival

Advances in Immunotherapy for Acute Myeloid Leukemia

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