In Vitro Killing of Colorectal Carcinoma Cells by Autologous Activated NK Cells is Boosted by Anti-Epidermal Growth Factor Receptor-induced ADCC Regardless of RAS Mutation Status
In this study, after confirmation that patients’ NK cells were not impaired in their cytotoxic activity, evaluated against long-term tumor cell lines, we evaluated their interactions with autologous mCRC cells. Molecular and phenotypical evaluation of mCRC cells, expanded in vitro from liver metastasis, showed that they expressed high levels of polio virus receptor and Nectin-2, whereas UL16-binding proteins were less expressed in all tumor samples evaluated. Two different patterns of MICA/B and HLA class I expression on the membrane of mCRC were documented; approximately half of mCRC patients expressed high levels of th...
Source: Journal of Immunotherapy - April 21, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Anti-IL-10–mediated Enhancement of Antitumor Efficacy of a Dendritic Cell–targeting MIP3α-gp100 Vaccine in the B16F10 Mouse Melanoma Model Is Dependent on Type I Interferons
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine...
Source: Journal of Immunotherapy - April 21, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Natural Compounds as Epigenetic Regulators of Human Dendritic Cell-mediated Immune Function
Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and are poised to capture antigen, migrate to draining lymphoid organs, and postmaturation process. Recent evidences have suggested that tumor microenvironment has an effect on DCs by inactivating various components of the immune system responsible for tumor clearance, eventually leading to tumorigenesis. This inactivation is owed to the epigenetic modifications [ie, microRNA (miRNA)] at the posttranscriptional level, thus regulating the differentiation patterns and functional behavior of DCs. Thus, need of the hour is to develop protoco...
Source: Journal of Immunotherapy - April 21, 2018 Category: Allergy & Immunology Tags: Review Article Source Type: research
Bullous Pemphigoid–like Skin Lesions and Overt Eosinophilia in a Patient With Melanoma Treated With Nivolumab: Case Report and Review of the Literature
We present in this paper the case of a 48-year-old patient with melanoma who developed bullous pemphigoid–like skin lesions along with fever, arthralgia and overt eosinophilia following adjuvant treatment with nivolumab. The condition was successfully treated with corticosteroids and a rechallenge with another anti-PD1 agent did not lead to recurrence of the skin lesions. We also reviewed the literature on the epidemiologic, clinical, and histopathologic characteristics of bullous pemphigoid as well as on the treatment and prognosis of this dermatologic condition in patients with melanoma or other malignancies under trea...
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation
Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas>1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteri...
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination With Ofatumumab After Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma
Interleukin-18 (IL-18) is an immunostimulatory cytokine that augments antibody-dependent cellular cytotoxicity mediated by human natural killer cells against antibody-coated lymphoma cells in vitro and that has antitumor activity in animal models. Ofatumumab is a CD20 monoclonal antibody with activity against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20+ lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Cohorts of 3 patients were given intravenous infusions of ofatumumab 1000 mg...
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Whole Recombinant Saccharomyces cerevisiae Yeast Expressing Ras Mutations as Treatment for Patients With Solid Tumors Bearing Ras Mutations: Results From a Phase 1 Trial
We are developing whole, heat-killed, recombinant Saccharomyces cerevisiae yeast, engineered to encode target proteins, which stimulate immune responses against malignant cells expressing those targets. This phase 1 trial, enrolling patients with advanced colorectal or pancreas cancer, was designed to evaluate safety, immunogenicity, response, and overall survival of ascending doses of the GI-4000 series of products, which express 3 different forms of mutated Ras proteins. The study enrolled 33 heavily pretreated subjects (14 with pancreas and 19 with colorectal cancer), whose tumors were genotyped before enrollment to ide...
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Preclinical Assessment of CAR T-Cell Therapy Targeting the Tumor Antigen 5T4 in Ovarian Cancer
Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome both quantitative and qualitative shortfalls of the host immune system relating to the detection and subsequent destruction of tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step in the ability to utilize CAR T cells for the treatment of cancer. The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer. Matched blood and tumor samples were collected from 12 patients with ovarian cancer; all tumors were positi...
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Brief Communication; A Heterologous Oncolytic Bacteria-Virus Prime-Boost Approach for Anticancer Vaccination in Mice
In this study, we show that Listeria monocytogenes can be used in place of the Ad to obtain comparable immune priming efficiency before MRB boosting. Importantly, the therapeutic benefits provided by our heterologous L. monocytogenes-MRB prime-boost strategy are superior to those conferred by the Ad-MRB combination. Our study provides proof of concept for the heterologous oncolytic bacteria-virus prime-boost approach for anticancer vaccination and merits its consideration for clinical testing. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
HMGN2: An Antitumor Effector Molecule of γδT Cells
This study suggests that HMGN2 is an antitumor effector molecule of γδT cells. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
NKG2D Immunoligand rG7S-MICA Enhances NK Cell-mediated Immunosurveillance in Colorectal Carcinoma
In conclusion, rG7S-MICA provides a novel immunotherapeutic strategy for CRC, which could be further developed against other CD24+ malignancies. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
The Risk of Diarrhea and Colitis in Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis
Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti–programmed death-1 (PD-1) or anti–cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis. Pooled incidence and weighted relative risk estimates with 95% confi...
Source: Journal of Immunotherapy - March 21, 2018 Category: Allergy & Immunology Tags: Review Article Source Type: research
Pneumonitis in Irradiated Lungs After Nivolumab: A Brief Communication and Review of the Literature
Nivolumab is a feasible therapy option in patients with advanced non–small cell lung cancer (NSCLC) who progress on first-line treatment. However, there is limited information about an overlapping toxicity of PD-1 inhibitors when administered following thoracic radiotherapy (TRT). Three of 25 patients with advanced NSCLC were treated with palliative or curative intent. Nivolumab was initiated as second or third-line therapy after TRT for recurrent or progressive disease. All 3 patients developed grade 3 pneumonitis at some point during nivolumab therapy. Herein, we describe 3 cases of pneumonitis in patients with NSCLC s...
Source: Journal of Immunotherapy - February 1, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Pembrolizumab Utilization and Outcomes for Advanced Melanoma in US Community Oncology Practices
The programmed death-1 inhibitor pembrolizumab has demonstrated efficacy and safety in clinical trials for treating advanced (unresectable/metastatic) melanoma. We investigated the real-world utilization of pembrolizumab and associated patient outcomes for advanced melanoma in US community oncology practices. This retrospective, observational study used deidentified data from electronic health records for adult patients with advanced melanoma who received pembrolizumab at The US Oncology Network sites from September 2014 through December 2015, with follow-up through September 2016. Patients enrolled in clinical trials were...
Source: Journal of Immunotherapy - February 1, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Significance of Immune-related Lipase Increase Induced by Antiprogrammed Death-1 or Death Ligand-1 Antibodies: A Brief Communication
Antiprogrammed death-1 (anti-PD1) and antiprogrammed death ligand-1 (anti-PD-L1) antibodies are effective checkpoint inhibitors that stimulate the immune system against many types of cancers. The flip side of these immunotherapies is the generation of immune-related adverse events, which can theoretically affect all organs. Among these side effects, lipase increase is frequently observed; however the meaning of this biological abnormality remains poorly understood. We investigate in this case study all the lipase increases greater or equal to grade 2 that occurred in patients receiving anti-PD-1 or anti-PD-L1 treatments, t...
Source: Journal of Immunotherapy - February 1, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
