We previously demonstrated that autologous natural killer (NK)-cell therapy after hematopoietic cell transplantation (HCT) is safe but does not provide an antitumor effect. We hypothesize that this is due to a lack of NK-cell inhibitory receptor mismatching with autologous tumor cells, which may be overcome by allogeneic NK-cell infusions. Here, we test haploidentical, related-donor NK-cell infusions in a nontransplantation setting to determine safety and in vivo NK-cell expansion. Two lower intensity outpatient immune suppressive regimens were tested: (1) low-dose cyclophosphamide and methylprednisolone and (2) fludarabine. A higher intensity inpatient regimen of high-dose cyclophosphamide and fludarabine (Hi-Cy/Flu) was tested in patients with poor-prognosis acute myeloid leukemia (AML). All patients received subcutaneous interleukin 2 (IL-2) after infusions. Patients who received lower intensity regimens showed transient persistence but no in vivo expansion of donor cells. In contrast, infusions after the more intense Hi-Cy/Flu resulted in a marked rise in endogenous IL-15, expansion of donor NK cells, and induction of complete hematologic remission in 5 of 19 poor-prognosis patients with AML. These findings suggest that hap...Continue Reading
A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone
Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors
Economic analyses of bone marrow and blood stem cell transplantation for leukemias and lymphoma: what do we know?
Activated peripheral blood mononuclear cells from patients receiving subcutaneous interleukin-2 following autologous stem cell transplantation prolong survival of SCID mice bearing human lymphoma
Regulation of human lymphocyte IL-4 secretion by intestinal epithelial cell-derived interleukin-7 and transforming growth factor-beta
Cytotoxic lymphocyte recognition of HLA-E: utilizing a nonclassical window to peer into classical MHC
Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer
Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population
Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells
Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2.
Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors.
IL-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase I/II trial
Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease
Role of KIR ligand incompatibility in hematopoietic stem cell transplantation using unrelated donors.
Phase I studies of interleukin (IL)-2 and rituximab in B-cell non-hodgkin's lymphoma: IL-2 mediated natural killer cell expansion correlations with clinical response
Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes
Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors
Immunotherapy in high-risk chemotherapy-resistant patients with metastatic solid tumors and hematological malignancies using intentionally mismatched donor lymphocytes activated with rIL-2: a phase I study
A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer
Chemotherapy-resistant osteosarcoma is highly susceptible to IL-15-activated allogeneic and autologous NK cells
Effect of the simultaneous administration of glucocorticoids and IL-15 on human NK cell phenotype, proliferation and function
Effective modulation of CD4(+)CD25 (+high) regulatory T and NK cells in malignant patients by combination of interferon-α and interleukin-2.
Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells
The narrow-spectrum HDAC inhibitor entinostat enhances NKG2D expression without NK cell toxicity, leading to enhanced recognition of cancer cells
Perspective on the role of haploidentical transplantation in the management of hematologic malignancies: why do it?
Novel approaches to prevent leukemia relapse following allogeneic hematopoietic cell transplantation
Ex vivo expansion of canine cytotoxic large granular lymphocytes exhibiting characteristics of natural killer cells
HLA-E upregulation on IFN-gamma-activated AML blasts impairs CD94/NKG2A-dependent NK cytolysis after haplo-mismatched hematopoietic SCT
Generation of donor natural killer cells from CD34(+) progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study
The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies
Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers
Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML
Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method
CD3+/CD19+-depleted grafts in HLA-matched allogeneic peripheral blood stem cell transplantation lead to early NK cell cytolytic responses and reduced inhibitory activity of NKG2A
Identifying candidate allogeneic NK-cell donors for hematopoietic stem-cell transplantation based on functional phenotype
IL-15-stimulated CD3/CD19-depleted stem-cell boosts in relapsed pediatric patients after haploidentical SCT
Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer
Clinical-scale single-step CD4(+) and CD8(+) cell depletion for donor innate lymphocyte infusion (DILI)
Activated natural killer cells from patients with acute myeloid leukemia are cytotoxic against autologous leukemic blasts in NOD/SCID mice
Involvement of mature donor T cells in the NK cell reconstitution after haploidentical hematopoietic stem-cell transplantation
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.
AML: Role of LSD1 by CRISPR (Keystone)
Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.
Cancer Biology: Molecular Imaging
Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.