NK Cell–derived Exosomes From NK Cells Previously Exposed to Neuroblastoma Cells Augment the Antitumor Activity of Cytokine-activated NK Cells
Immune cell–derived exosomes can increase immunity against tumors. In contrast, tumor-derived exosomes can reduce the immunity and can change the tumor microenvironment to further develop and provide metastasis. These effects take place by an alteration in the innate and adaptive immune cell functions. In this experiment, we studied the natural killer (NK) cells’ effectiveness on tumor cells after expansion and thereafter incubated it with exosomes. The exosomes were derived from 2 populations of NK cells: (1) naive NK cells and, (2) NK cells previously exposed to neuroblastoma (NB) cells. Moreover, we have studied the...
Source: Journal of Immunotherapy - August 23, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Ex Vivo Induction of Multiple Myeloma-specific Immune Responses by Monocyte-derived Dendritic Cells Following Stimulation by Whole-tumor Antigen of Autologous Myeloma Cells
The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo–generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irr...
Source: Journal of Immunotherapy - August 23, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Diabetic Ketoacidosis as an Immune-related Adverse Event from Pembrolizumab in Non–Small Cell Lung Cancer
Programmed cell death protein 1 pathway inhibitors are now routinely administered to patients with non–small cell lung cancer, and prompt recognition of immune-related adverse events is critical to managing serious drug toxicities. Here, we describe a 66-year-old man with no known history of diabetes who presented with diabetic ketoacidosis after receiving 3 doses of pembrolizumab for lung adenocarcinoma. Autoimmune diabetes is a rare but potentially life-threatening complication of programmed cell death protein 1 inhibitors (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - July 1, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Significance of Frequencies, Compositions, and/or Antileukemic Activity of (DC-stimulated) Invariant NKT, NK and CIK Cells on the Outcome of Patients With AML, ALL and CLL
Invariant natural killer T (iNKT)/natural killer (NK)/cytokine-induced killer (CIK) cells are important for immune surveillance. (I) Novel combinations of antibody 6B11 (targeting the Vα24-Jα18-invariant T-cell receptor) with CD4/CD8/CD1d/Vα24 for iNKT subset detection and “T/NK cell-like”-iNKT subsets were defined. Compared with healthy peripheral blood mononuclear cells (MNC) (significantly) lower proportions of iNKT cells (6B11+/6B11+CD3+/6B11+CD161+), NK cells (CD3−CD56+/CD3−CD161+), and CIK cells (CD3+CD56+/CD3+CD161+) were found in peripheral blood MNC from acute myeloid (AML)/acute myeloid, lymphoid (ALL)...
Source: Journal of Immunotherapy - July 1, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Inflammatory Myopathy and Axonal Neuropathy in a Patient With Melanoma Following Pembrolizumab Treatment
In this report, we present a unique case of a patient with a complex neuromyopathic syndrome with axonal neuropathy and inflammatory myopathy after a single dose of pembrolizumab. An 82-year-old patient with a previously untreated stage IIIc melanoma developed ptosis in the left eye, generalized weakness, and neck and shoulder pain 15 days after pembrolizumab administration. He had left-sided ptosis and miosis, with a normal pupillary light reflex, horizontal diplopia, and voice hoarseness, along with weakness of the neck muscles and a hypokinetic right vocal cord at laryngoscopy. The laboratory evaluation was remarkable f...
Source: Journal of Immunotherapy - July 1, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Zebularine Treatment Induces MAGE-A11 Expression and Improves CTL Cytotoxicity Using a Novel Identified HLA-A2-restricted MAGE-A11 Peptide
In this study, a series of HLA-A2-restricted candidate MAGE-A11 peptides were predicted, synthesized, and tested. Of the selected peptides, p350 (FLFGEPKRL) elicited peptide-specific CTLs from healthy HLA-A*0201-positive donors. The induced CTLs can lyse MAGE-A11-expressing breast cancer cells but not MAGE-A11-negative tumor cells. To improve antitumor immune response, zebularine, a DNA methyltransferase inhibitor, was used to induce MAGE-A11 expression and upregulate the cytotoxicity of antigen-specific T cells in breast cancer cell lines and primary breast cancer cells. The present findings suggested that peptide p350 in...
Source: Journal of Immunotherapy - July 1, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Antigen Presentation by Individually Transferred HLA Class I Genes in HLA-A, HLA-B, HLA-C Null Human Cell Line Generated Using the Multiplex CRISPR-Cas9 System
Human leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and ...
Source: Journal of Immunotherapy - July 1, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Ipilimumab-induced Guillain-Barré Syndrome Presenting as Dysautonomia: An Unusual Presentation of a Rare Complication of Immunotherapy
Immune-related adverse events are common and well-documented in patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 monoclonal antibody approved for the treatment of metastatic and stage III melanoma. Neurological complications are rare, but widely variable and potentially devastating. Here, we discuss a case of a patient who was treated with a single dose of ipilimumab for resected stage III melanoma. She subsequently developed pandysautonomia that manifested as a tonically dilated pupil, gastrointestinal dysmotility, urinary retention, and profound orthostatic hypotension. Guillain-Barré syndrome was di...
Source: Journal of Immunotherapy - May 10, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
CD19 Isoforms Enabling Resistance to CART-19 Immunotherapy Are Expressed in B-ALL Patients at Initial Diagnosis
In conclusion, we proved that some of the CD19 isoforms contributing to CART-19 escape already preexist at diagnosis and could evolve as a dominant clone during CART-19 therapy suggesting the application of combined treatment approaches. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 10, 2017 Category: Allergy & Immunology Tags: Clinical Study Source Type: research
Transforming Growth Factor β is a Poor Prognostic Factor and Inhibits the Favorable Prognostic Value of CD8+ CTL in Human Hepatocellular Carcinoma
In conclusion, our study suggests that TGF-β is a poor prognostic factor for patients and negatively affect the prognostic value of CD8+ CTLs through suppressing antitumor activity of CD8+ T-cell in HCC. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 10, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Sunitinib Induces NK-κB-dependent NKG2D Ligand Expression in Nasopharyngeal Carcinoma and Hepatoma Cells
In this study, we confirmed sunitinib induced downregulation of its targets, such as vascular endothelial growth factor, platelet-derived growth factor, and c-kit in multiple-drug–resistant nasopharyngeal carcinoma cell line CNE2/DDP and hepatoma cell line HepG2. Then, we further showed sunitinib induced cell proliferation inhibition, apoptosis, and DNA damage in CNE2/DDP and HepG2 cells. Coculture experiments showed that sunitinib-treated CNE2/DDP and HepG2 cells were able to increase the activation and cytotoxicity of NK cells. Quantitative polymerase chain reaction results showed that sunitinib upregulated NKG2DLs, ap...
Source: Journal of Immunotherapy - May 10, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Ubiquitinated Proteins Isolated From Tumor Cells Are Efficient Substrates for Antigen Cross-Presentation
We have previously shown that inhibition of the proteasome causes defective ribosomal products to be shunted into autophagosomes and subsequently released from tumor cells as defective ribosomal products in Blebs (DRibbles). These DRibbles serve as an excellent source of antigens for cross-priming of tumor-specific T cells. Here, we examine the role of ubiquitinated proteins (Ub-proteins) in this pathway. Using purified Ub-proteins from tumor cells that express endogenous tumor-associated antigen or exogenous viral antigen, we tested the ability of these proteins to stimulate antigen-specific T-cell responses, by activatio...
Source: Journal of Immunotherapy - May 10, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Treatment of Cervical Intraepithelial Neoplasia: Patients Preferences for Surgery or Immunotherapy with Imiquimod
This study aims to investigate womens’ preferences for treatment of high-grade CIN with imiquimod or LLETZ. A labeled discrete choice experiment was conducted among 100 women with abnormal cervical cytology in 5 hospitals in the Netherlands between March 2014 and December 2015. Participants were asked to choose between imiquimod treatment or standard surgical treatment in 9 separate scenarios, based on the following treatment characteristics: treatment success rate, rate of side effects, risk of premature birth in subsequent pregnancies, and risk of subfertility after treatment. The levels of these characteristics differ...
Source: Journal of Immunotherapy - April 12, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC
We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response. Vaccine-related adverse events observed were fever and injection-s...
Source: Journal of Immunotherapy - April 12, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer
We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated...
Source: Journal of Immunotherapy - April 12, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
