Ex vivo-expanded NK cells from blood and ascites of ovarian cancer patients are cytotoxic against autologous primary ovarian cancer cells

AbstractOvarian cancer (OC) is the leading cause of gynecological cancer-related death in North America. Most ovarian cancer patients (OCPs) experience disease recurrence after first-line surgery and chemotherapy; thus, there is a need for novel second-line treatments to improve the prognosis of OC. Although peripheral blood-derived NK cells are known for their ability to spontaneously lyse tumour cells without prior sensitization, ascites-derived NK cells (ascites-NK cells) isolated from OCPs exhibit inhibitory phenotypes, impaired cytotoxicity and may play a pro-tumourigenic role in cancer progression. Therefore, it is of interest to improve the cytotoxic effector function of impaired OCP ascites-NK cells at the tumour environment. We investigated the efficacy of using an artificial APC-based ex vivo expansion technique to generate cytotoxic, expanded NK cells from previously impaired OCP ascites-NK cells, for use in an autologous model of NK cell immunotherapy. We are the first to obtain a log-scale expansion of OCP ascites-NK cells that upregulate the surface expression of activating receptors NKG2D, NKp30, NKp44, produce robust amounts of anti-tumour cytokines in the presence of OC cells and mediate direct tumour cytotoxicity against ascites-derived, primary OC cells obtained from autologous patients. Our findings demonstrate that it is possible to generate cytotoxic OCP ascites-NK cells from previously impaired OCP ascites-NK cells, which presents a promising immunother...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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AbstractPARP (poly(ADP-ribose) polymerase) inhibitors represent a novel class of anti-cancer therapy; they take advantage of synthetic lethality and induce cell death by exploiting a defect in DNA repair. This class of medication was initially evaluated in patients with BRCA-associated tumors, but efficacy was also demonstrated in other populations. Since 2014, four PARP inhibitors have been approved in various indications: olaparib, niraparib, and rucaparib in high-grade serous ovarian cancer, and olaparib and talazoparib in metastatic breast cancer. The exact indications and study populations vary slightly between the di...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThese results indicate the viability of TIL ACT for refractory ovarian cancer by allowing for the large expansion of anti-tumor TIL in a short time and consistent manner.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
A mesothelioma patient at West Cancer Center in Memphis, Tennessee, is the first in the country to use NovoTTF-100L, a noninvasive electric therapy treatment, since its approval by the U.S. Food and Drug Administration in May. The FDA’s approval of Novocure’s Tumor Treating Fields device for the treatment of mesothelioma marked the first new FDA-approved treatment option for the rare asbestos-related cancer in more than 15 years. NovoTTF-100L uses a low-voltage electrical field that is distributed with three pads attached to the front and back of a person’s chest. The electrical current is designed to di...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
This report describes a patient whose presenting complaints were “Physical examination showed that the pancreas was occupied for one month.” He initially was diagnosed with stage IV PC based on conventional imaging and pathologic assessment. He had a known germline BRCA 2 mutation, which exhibited a good response to PARP inhibitor therapy. Diagnosis: Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation. Interventions: He received gemcitabine and albumin-bound paclitaxel chemotherapy from March 15, 2017 to...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
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Source: OncoImmunology - Category: Cancer & Oncology Authors: Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract OBJECTIVES: Immune checkpoint inhibitors (ICIs) have modest activity in ovarian cancer (OC), yet little is known about their effects on subsequent treatment. Preclinical studies suggest immunotherapy may enhance response to chemotherapy. We sought to evaluate the impact of ICIs on subsequent therapies and survival in recurrent OC. METHODS: A retrospective review was conducted to identify women with recurrent OC who received ICI from 01/2013 to 5/2017 and ≥1 subsequent treatment. Treatment duration after ICI was calculated using time-to-event analysis. Kaplan-Meier survival analysis and Cox proport...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
ConclusionsThis work highlights the importance of CD4+ T cells in tumor immunology. Furthermore, the data support the initiation of clinical trials in ovarian cancer that target both innate and adaptive immunity, with a focus on optimizing dosing schedules.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractA pilot study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer has been started in Korea. Archival tumor samples were tested for HRD and PD-L1 status. Treatment arms will be allocated according to the test results. For HRD+ patients, we tested the synergistic effects of olaparib and other agents; treatment arms will randomly be allocated. (Arm 1: olaparib and cediranib; Arm 2: olaparib and durvalumab). For HRD- patients, we tested the role of biomarker-driven immunotherapy according to PD-L1 expression (Arm 3: durvalumab and chemotherapy in patients with high PD-L1 e...
Source: Japanese Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
Advanced ovarian cancer is frequently treated with combination chemotherapy, but high recurrence rates show the need for therapies that can produce durable responses and extend overall survival. Bispecific antibodies that interact with tumor antigens on cancer cells and activating receptors on immune cells offer an innovative immunotherapy approach. Here, we describe a human bispecific antibody (REGN4018) that binds both Mucin 16 (MUC16), a glycoprotein that is highly expressed on ovarian cancer cells, and CD3, thus bridging MUC16-expressing cells with CD3+ T cells. REGN4018 induced T cell activation and killing of MUC16-e...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
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