Cytotoxic Activity and Memory T Cell Subset Distribution of in vitro-Stimulated CD8+ T Cells Specific for HER2/neu Epitopes

Minimal residual disease remaining after resection of primary tumors can lead to tumor recurrence and metastasis, increasing mortality and morbidity rates among cancer patients. Thus, there is a need for new technologies for recognition and elimination of single cancer cells remaining in a patient’s body after radiation therapy, chemotherapy, or surgical resection. Effector CD8+ T cells, also commonly known as cytotoxic T lymphocytes (CTLs), play a key role in antitumor cellular immunity and, when properly activated, are able to effectively destroy tumor cells. The aims of this study were to obtain CD8+ CTLs specific for the HER2/neu epitopes E75 and E88, and to assess the cytotoxic activity and composition of these cells in terms of the distribution of memory T-cell subsets. We obtained HER2-specific CD8+ T cells and assessed T cell subset distribution among them including naive T cells (TN), central memory T cells (TCM), effector memory T cells (TEM), stem cell-like memory T cells (TSCM) and terminally-differentiated T cells (TEMRA) via eight-color flow cytometry. HER2-specific CTLs were largely (~40–50%) represented by TSCM cells, a population capable of mounting pronounced antitumor immune responses due to a combination of effector function and self-maintenance. In comparison with activated peripheral blood mononuclear cells (PBMCs) and bulk CD8+ T cells, HER2-specific CTLs exhibited greater cytotoxicity against the HER2-expressing human breast adenocarcinoma ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Late recurrence of estrogen receptor (ER) positive breast cancer is common. When tissues from a recurrent or metastatic focus are available, re-evaluation of ER, progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status is recommended for treatment selection. This case report describes a 59-year-old woman who underwent surgery for left breast cancer, with a histopathological diagnosis of invasive ductal carcinoma (pathological stage T2N1aM0 Stage IIB, ER positive, PgR positive and HER2 negative). A health check-up 16 years after surgery revealed multiple hepatic mass lesions, and the patient w...
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
Amgen (NASDAQ:AMGN) and Allergan plc (NYSE:AGN) announced that the U.S. Food and Drug Administration (FDA) has approved KANJINTITM (trastuzumab-anns) for all approved indications of the reference product, Herceptin® (trastuzumab): for the treatment of HER2-overexpressing adjuvant and metastatic breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.
Source: World Pharma News - Category: Pharmaceuticals Tags: Featured Amgen Business and Industry Source Type: news
Approval Based on Totality of Evidence Demonstrating KANJINTI is Biosimilar to Herceptin Third FDA Approval From Amgen's Biosimilars Portfolio THOUSAND OAKS, Calif., June 13, 2019 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and Allergan plc (NYSE:AGN) today announced that the U.S. Food and Drug Administration (FDA) has approved KANJINTI™ (trastuzumab-anns) for all approved indications of the reference product, Herceptin® (trastuzumab):  for the treatment of HER2-overexpressing adjuvant and metastatic breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. "...
Source: Amgen News Release - Category: Pharmaceuticals Tags: Uncategorized Source Type: news
Publication date: Available online 6 June 2019Source: The LancetAuthor(s): Xavier Pivot, Gilles Romieu, Marc Debled, Jean-Yves Pierga, Pierre Kerbrat, Thomas Bachelot, Alain Lortholary, Marc Espié, Pierre Fumoleau, Daniel Serin, Jean-Philippe Jacquin, Christelle Jouannaud, Maria Rios, Sophie Abadie-Lacourtoisie, Laurence Venat-Bouvet, Laurent Cany, Stéphanie Catala, David Khayat, Laetitia Gambotti, Iris PauportéSummaryBackgroundIn 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-...
Source: The Lancet - Category: General Medicine Source Type: research
This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
We present three cases of patients definitively treated for osteosarcoma who subsequently developed a second malignant neoplasm. The first case describes a 17-year-old female with osteosarcoma of her right femur treated with surgical resection and perioperative chemotherapy. Ten years later, she was diagnosed with metastatic HER2-positive breast cancer. Genetic testing identified a germline TP53 mutation, confirming the presence of Li-Fraumeni syndrome. The second case details an 18-year-old male with osteosarcoma of his right humerus treated with definitive resection and perioperative chemotherapy. He was diagnosed with a...
Source: Irish Journal of Medical Science - Category: General Medicine Source Type: research
Charles Saby1, Guillaume Collin1, Maha Sinane1, Emilie Buache1, Laurence Van Gulick1, Frédéric Saltel2, Erik Maquoi3† and Hamid Morjani1*† 1Unité BioSpecT, EA7506, SFR CAP-Santé, UFR de Pharmacie, Université de Reims Champagne-Ardenne, Reims, France 2INSERM, UMR1053, BaRITOn Bordeaux Research in Translational Oncology, Bordeaux, France 3Unit of Cancer, Laboratory of Tumour and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué (GIGA), University of Liège, Liège, Belgium Type I collagen is the major adhe...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we evaluated the therapeutic benefit of combining the TAB004 antibody with Liposomal-MSA-IL-2 in immune competent and human MUC1 transgenic (MUC1.Tg) mouse models of PDA and investigated the associated immune responses. Treatment with TAB004 + Lip-MSA-IL-2 resulted in significantly improved survival and slower tumor growth compared to controls in MUC1.Tg mice bearing an orthotopic PDA.MUC1 tumor. Similarly, in the spontaneous model of PDA that expresses human MUC1, the combination treatment stalled the progression of pancreatic intraepithelial pre-neoplastic (PanIN) lesion to adenocarcinoma. Treatment with t...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: This meta-analysis demonstrated that CD44 overexpression might be an unfavorable prognostic factor for CRC patients and could be used to predict poor differentiation, lymph node metastasis and distant metastasis. Introduction Although therapies for colorectal cancer (CRC) has improved in recent years, colorectal cancer is still the third most common cause of cancer related death worldwide (1). Metastasis are observed in 25% of patients at initial diagnosis and approximately 50% of patients will develop metastasis (2). Presently, the outcome prediction and the therapy schedule determination of CRC patie...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: The newly developed radiomic signature was a powerful predictor of LN metastasis and the radiomics nomogram could facilitate the preoperative individualized prediction of LN status. Introduction Gastric cancer (GC) is one of the most common malignant tumors and the second leading cause of cancer-related deaths worldwide (1). Accurate evaluation of lymph node metastasis (LNM) status in GC patients is vital for prognosis and treatment decisions (2–4). Some histopathologic factors and biomarkers (e.g., lymphatic invasion, matrix metalloproteinase-2) are found to be able to predict LNM in GC, but mos...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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