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Pancreatic cancer immunotherapy

Yoichi Kato
We assessed the efficacy of WT1 class I peptide and WT1 class II peptide pulsed dendritic cell(DC)therapy for a wide range of advanced cancers. This retrospective study included 60 advanced cancer patients who were vaccinated 5times or more in this clinic between September 2013 and December 2015. The clinical response was examined. This treatment was approved by the ethics panel at this institution. Sixty patients were injected an average of 6.15times with dendritic cells(DCs) (2.6×10 / 7 cells/injection)...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Vanaja Konduri, Dali Li, Matthew M Halpert, Dan Liang, Zhengdong Liang, Yunyu Chen, William E Fisher, Silke Paust, Jonathan M Levitt, Qizhi Cathy Yao, William K Decker
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, exhibiting a five-year overall survival (OS) of only 7% despite aggressive standard of care. Recent advances in immunotherapy suggest potential application of immune-based treatment approaches to PDAC. To explore this concept further, we treated orthotopically established K-ras(G12D)/p53(-/-) PDAC tumors with gemcitabine and a cell-based vaccine previously shown to generate durable cell-mediated (TH1) immunity...
2016: Oncoimmunology
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
October 4, 2016: Oncotarget
Emma Eriksson, Jessica Wenthe, Sandra Irenaeus, Angelica Loskog, Gustav Ullenhag
BACKGROUND: Cancer immunotherapy can be potentiated by conditioning regimens such as cyclophosphamide, which reduces the level of regulatory T cells (tregs). However, myeloid suppressive cells are still remaining. Accordingly to previous reports, gemcitabine improves immune status of cancer patients. In this study, the role of gemcitabine was further explored to map its immunological target cells and molecules in patients with pancreatic cancer. METHODS: Patient blood was investigated by flow cytometry and cytokine arrays at different time points during gemcitabine treatment...
September 29, 2016: Journal of Translational Medicine
Rebecca A Evans, Mark S Diamond, Andrew J Rech, Timothy Chao, Max W Richardson, Jeffrey H Lin, David L Bajor, Katelyn T Byrne, Ben Z Stanger, James L Riley, Nune Markosyan, Rafael Winograd, Robert H Vonderheide
In carcinogen-driven cancers, a high mutational burden results in neoepitopes that can be recognized immunologically. Such carcinogen-induced tumors may evade this immune response through "immunoediting," whereby tumors adapt to immune pressure and escape T cell-mediated killing. Many tumors lack a high neoepitope burden, and it remains unclear whether immunoediting occurs in such cases. Here, we evaluated T cell immunity in an autochthonous mouse model of pancreatic cancer and found a low mutational burden, absence of predicted neoepitopes derived from tumor mutations, and resistance to checkpoint immunotherapy...
September 8, 2016: JCI Insight
Sonja Textor, Felicitas Bossler, Kai-Oliver Henrich, Moritz Gartlgruber, Julia Pollmann, Nathalie Fiegler, Annette Arnold, Frank Westermann, Nina Waldburger, Kai Breuhahn, Sven Golfier, Mathias Witzens-Harig, Adelheid Cerwenka
Natural Killer (NK) cells are innate effector cells that are able to recognize and eliminate tumor cells through engagement of their surface receptors. NKp30 is a potent activating NK cell receptor that elicits efficient NK cell-mediated target cell killing. Recently, B7-H6 was identified as tumor cell surface expressed ligand for NKp30. Enhanced B7-H6 mRNA levels are frequently detected in tumor compared to healthy tissues. To gain insight in the regulation of expression of B7-H6 in tumors, we investigated transcriptional mechanisms driving B7-H6 expression by promoter analyses...
July 2016: Oncoimmunology
Awalpreet S Chadha, Allison Khoo, Maureen L Aliru, Harpreet K Arora, Jillian R Gunther, Sunil Krishnan
The outcomes for treatment of pancreatic cancer have not improved dramatically in many decades. However, the recent promising results with combination chemotherapy regimens for metastatic disease increase optimism for future treatments. With greater control of overt or occult metastatic disease, there will likely be an expanding role for local treatment modalities, especially given that nearly a third of pancreatic cancer patients have locally destructive disease without distant metastatic disease at the time of death...
October 2016: Seminars in Radiation Oncology
Catalina Mosquera, Dino Maglic, Emmanuel E Zervos
Molecular targeted therapy is widely utilized and effective in a number of solid tumors. In pancreatic adenocarcinoma, targeted therapy has been extensively evaluated; however, survival improvement of this aggressive disease using a targeted strategy has been minimal. The purpose of this study is to review therapeutic molecular targets in completed and ongoing later phase (II and III) clinical trials to have a better understanding of the rationale and progress towards targeted molecular therapies for pancreatic cancer...
August 2, 2016: Cancer Genetics
Omid Haji-Ghassemi, Michel Gilbert, Jenifer Spence, Melissa J Schur, Matthew J Parker, Meredith L Jenkins, John E Burke, Henk van Faassen, N Martin Young, Stephen V Evans
Aberrant glycosylation and the overexpression of specific carbohydrate epitopes is a hallmark of many cancers, and tumor-associated oligo-saccharides are actively investigated as targets for immunotherapy and diagnostics. Wisteria floribunda agglutinin (WFA) is a legume lectin that recognizes terminal N-acetylgalactosaminides with high affinity. WFA preferentially binds the disaccharide LacdiNAc (β-D-GalNAc-[1→4]-D-GlcNAc), which is associated with tumor malignancy in leukemia, prostate, pancreatic, ovarian, and liver cancers, and has shown promise in cancer glycobiomarker detection...
September 6, 2016: Journal of Biological Chemistry
Xin Wang, Feifei Teng, Li Kong, Jinming Yu
PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial...
2016: OncoTargets and Therapy
Athanasios Petrou, Demetrios Moris, Patrick Paul Tabet, Brian David Wensley Richards, Georgios Kourounis
Pancreatic ductal adenocarcinoma is a lethal and late presenting malignancy with dismal survival rates. An estimated total of 330,000 people died from this malignancy in 2012. Although there have been improvements in diagnostic and treatment methods, the survival of late stage pancreatic cancer has not shown significant improvement in the past 4 decades. Multiple treatment approaches are available including chemotherapy, radiotherapy, and immunotherapy, but to this day surgical resection remains the only curative treatment option...
May 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Satoshi Matsukuma, Kiyoshi Yoshimura, Tomio Ueno, Atsunori Oga, Moeko Inoue, Yusaku Watanabe, Atsuo Kuramasu, Masanori Fuse, Ryoichi Tsunedomi, Satoshi Nagaoka, Hidetoshi Eguchi, Hiroto Matsui, Yoshitaro Shindo, Noriko Maeda, Yoshihiro Tokuhisa, Reo Kawano, Tomoko Furuya-Kondo, Hiroshi Itoh, Shigefumi Yoshino, Shoichi Hazama, Masaaki Oka, Hiroaki Nagano
Cancer stem-like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P-CSLCs). P-CSLC-enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by two-dimensional electrophoresis and tandem mass spectrometry...
August 25, 2016: Cancer Science
Jianda Yuan
Immune checkpoint blockade therapies are revolutionizing standard cancer treatments. Immune checkpoint inhibitors likely function to enhance the tumor specific antigen response in order to achieve favorable clinical outcomes. Thus, continuous efforts to identify the common tumor-specific antigens are essential for the broad clinical application of these therapies. Several immunoproteomics approaches have been used in order to screen for this specificity. In a recent article from Jhaveri and colleagues published in the February issue of Cancer Immunology Research, antibody biomarkers were screened in pancreatic cancer patients who received allogeneic, granulocyte-macrophage colony stimulating factor-secreting pancreatic cancer vaccine (GVAX) by using a serum antibody-based SILAC immunoprecipitation (SASI) approach...
2016: Journal for Immunotherapy of Cancer
Cristina Jimenez-Luna, Jose Prados, Raul Ortiz, Consolacion Melguizo, Carolina Torres, Octavio Caba
Pancreatic cancer (PC) is a lethal disease representing the seventh most frequent cause of death from cancer worldwide. Resistance of pancreatic tumors to current treatments leads to disappointing survival rates, and more specific and effective therapies are urgently needed. In recent years, immunotherapy has been proposed as a promising approach to the treatment of PC, and encouraging results have been published by various preclinical and clinical studies. This review provides an overview of the latest developments in the immunotherapeutic treatment of PC and summarizes the most recent and important clinical trials...
November 2016: Journal of Clinical Gastroenterology
Paola Cappello, Elisabetta Tonoli, Roberta Curto, Daniele Giordano, Mirella Giovarelli, Francesco Novelli
Pancreatic Ductal Adenocarcinoma (PDA) is a very aggressive tumor for which effective therapeutical strategies are still lacking. Globally, the 5 y survival rate is 5-7% and surgery is the only potentially curative treatment. Immunotherapy represents a novel possibility for treating PDA, and myeloid-derived suppressor cells (MDSC), which are increased in cancer patients and correlate with metastatic burden and cancer stage, offer a new target in cancer therapy. We have previously shown that antibodies against the PDA-associated antigen α-enolase (ENO1) are detected in more than 60% of PDA patients and correlate with a better prognosis...
May 2016: Oncoimmunology
Hidenori Takahashi, Shigetaka Shimodaira, Masahiro Ogasawara, Shuichi Ota, Masanori Kobayashi, Hirofumi Abe, Yuji Morita, Kazuhiro Nagai, Shunichi Tsujitani, Masato Okamoto, Yukio Suzuki, Yoichi Nakanishi, Yoshikazu Yonemitsu
OBJECTIVE: The J-SICT DC Vaccine Study Group provides dendritic cell (DC) vaccines for compassionate use under unified cell production and patient treatment regimens. We previously reported beneficial effects of DC vaccines on the overall survival of 62 patients with advanced non-small cell lung cancer (NSCLC) in a single-center analysis. Here, we extended analysis to 260 patients with NSCLC who were treated at six centers. METHODS: Of the 337 patients who met the inclusion criteria, we analyzed 260 patients who received ≥5 peptide-pulsed DC vaccinations once every 2 weeks...
September 2016: Cancer Immunology, Immunotherapy: CII
Peter Sidaway
No abstract text is available yet for this article.
September 2016: Nature Reviews. Clinical Oncology
Michail Karanikas, Agis Esempidis, Zeinep Tzoutze Memet Chasan, Theodora Deftereou, Maria Antonopoulou, Ferdi Bozali, Kyriakos Amarantidis, Yan-Gao Man
Pancreatic cancer is considered one of the most lethal malignances. It has been observed that the five year survival rate is less than 5%. Early diagnosis, understanding the risk factors and investigation of the molecular pathways with targeted therapy are the keys for efficient treatment. Moreover; there are several local treatments for patients with unresectable pancreatic cancer. There are several combined therapies with chemotherapy and radiotherapy, however; a local therapy approach for many patients with poor performance status are in need...
2016: Journal of Cancer
Hong Jiang, Samarth Hegde, Brett L Knolhoff, Yu Zhu, John M Herndon, Melissa A Meyer, Timothy M Nywening, William G Hawkins, Irina M Shapiro, David T Weaver, Jonathan A Pachter, Andrea Wang-Gillam, David G DeNardo
Single-agent immunotherapy has achieved limited clinical benefit to date in patients with pancreatic ductal adenocarcinoma (PDAC). This may be a result of the presence of a uniquely immunosuppressive tumor microenvironment (TME). Critical obstacles to immunotherapy in PDAC tumors include a high number of tumor-associated immunosuppressive cells and a uniquely desmoplastic stroma that functions as a barrier to T cell infiltration. We identified hyperactivated focal adhesion kinase (FAK) activity in neoplastic PDAC cells as an important regulator of the fibrotic and immunosuppressive TME...
August 2016: Nature Medicine
Wenxin Zheng, Kinga B Skowron, Jukes P Namm, Byron Burnette, Christian Fernandez, Ainhoa Arina, Hua Liang, Michael T Spiotto, Mitchell C Posner, Yang-Xin Fu, Ralph R Weichselbaum
The majority of cancer patients respond poorly to either vaccine or checkpoint blockade, and even to the combination of both. They are often resistant to high doses of radiation therapy as well. We examined prognostic markers of immune cell infiltration in pancreatic cancer. Patients with low CD8+ T cell infiltration and high PD-L1 expression (CD8+ TloPD-L1hi) experienced poor outcomes. We developed a mouse tumor fragment model with a trackable model antigen (SIYRYYGL or SIY) to mimic CD8+ TloPD-L1hi cancers...
June 13, 2016: Oncotarget
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