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Tumor specific antigens

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https://www.readbyqxmd.com/read/29456538/an-uncoupling-of-canonical-phenotypic-markers-and-functional-potency-of-ex-vivo-expanded-natural-killer-cells
#1
Nicole A P Lieberman, Kole DeGolier, Kristen Haberthur, Harrison Chinn, Kara W Moyes, Myriam N Bouchlaka, Kirsti L Walker, Christian M Capitini, Courtney A Crane
Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and ex vivo -expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to the elimination of tumor cells. Clinical efforts have also demonstrated limitations, however, including the potential for tumor cell antigenic drift and neoantigen formation, which promote tumor escape and recurrence, as well as rapid onset of T cell exhaustion in vivo . These findings suggest that antigen unrestricted cells, such as natural killer (NK) cells, may be beneficial for use as an alternative to or in combination with T cell based approaches...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456158/autologous-ipsc-based-vaccines-elicit-anti-tumor-responses-in-vivo
#2
Nigel G Kooreman, Youngkyun Kim, Patricia E de Almeida, Vittavat Termglinchan, Sebastian Diecke, Ning-Yi Shao, Tzu-Tang Wei, Hyoju Yi, Devaveena Dey, Raman Nelakanti, Thomas P Brouwer, David T Paik, Idit Sagiv-Barfi, Arnold Han, Paul H A Quax, Jaap F Hamming, Ronald Levy, Mark M Davis, Joseph C Wu
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models...
February 8, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29455841/actual-10-year-survival-after-hepatic-resection-of-colorectal-liver-metastases-what-factors-preclude-cure
#3
John M Creasy, Eran Sadot, Bas Groot Koerkamp, Joanne F Chou, Mithat Gonen, Nancy E Kemeny, Vinod P Balachandran, T Peter Kingham, Ronald P DeMatteo, Peter J Allen, Leslie H Blumgart, William R Jarnagin, Michael I D'Angelica
BACKGROUND: Hepatic resection of colorectal liver metastases is associated with long-term survival. This study analyzes actual 10-year survivors after resection of colorectal liver metastases, reports the observed rate of cure, and identifies factors that preclude cure. METHODS: A single-institution, prospectively maintained database was queried for all initial resections for colorectal liver metastases for the years 1992-2004. Observed cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up...
February 15, 2018: Surgery
https://www.readbyqxmd.com/read/29455318/expression-of-terminal-deoxynucleotidyl-transferase-tdt-in-classical-seminoma-a-potential-diagnostic-pitfall
#4
Alexander Brobeil, Florian Wagenlehner, Stefan Gattenlöhner
Seminomas are the most frequent testicular tumors and in spite of specific markers some histological subtypes can be diagnostically challenging due to the potential overlap of morphologic features and a variant antigen expression. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase present in hematogones, thymic T cells, lymphoblastic lymphoma/leukemia (LBL), and in some cases of acute myeloid leukemia but so far has not been described to be expressed in seminomas. After observing a reactivity of TdT in one case of seminoma, we analyzed ten additional tumors by immunohistochemistry to determine their spectrum of reactivity for TdT...
February 18, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29455299/prostate-specific-membrane-antigen-in-breast-cancer-a-comprehensive-evaluation-of-expression-and-a-case-report-of-radionuclide-therapy
#5
Yuri Tolkach, Heidrun Gevensleben, Ralph Bundschuh, Aydan Koyun, Daniela Huber, Christina Kehrer, Thomas Hecking, Mignon-Denise Keyver-Paik, Christina Kaiser, Hojjat Ahmadzadehfar, Markus Essler, Walther Kuhn, Glen Kristiansen
PURPOSE: Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized. METHODS: This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9...
February 17, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29454548/correlation-between-molecular-tumor-volume-evaluated-with-68-ga-psma-pet-ct-and-prostatic-specific-antigen-levels
#6
S Medina-Ornelas Sevastián, O García-Pérez Francisco, Y Hernández-Pedro Norma, E Arellano-Zarate Angélica, L Abúndiz-López Blanca
OBJECTIVE: To investigate the association between prostatic-specific antigen (PSA) levels and molecular tumor volume (MTV) measured in the68 Ga-PSMA PET/CT, both done in a short period of time, in prostate cancer patients with biochemical failure. METHODS: Eighty-four patients who underwent68 Ga-PSMA PET/CT and measurement of PSA levels in the same week (trigger-PSA) were studied in this retrospective analysis. MTV was calculated from the sum of the metastatic lesions...
February 14, 2018: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/29453962/an-autoantibody-against-human-dna-topoiomerase-i-is-a-novel-biomarker-for-non-small-cell-lung-cancer
#7
Wen-Bin Wu, Shang-Mian Yie, Shang-Rong Ye, Ke Xie, Jian-Bo Zhang, Mei Cao, Jie Chen, Xu He, Xiao-Li Ma, Jia Zhang
BACKGROUND: We previously reported a novel tumor associated antigen with a molecular weight around 48 kDa that was a fragment derived from human DNA-topoiomerase I. The aim of this study is to further investigate the clinical significance of the autoantibody in patients with non-small cell lung cancer (NSCLC). METHODS: We determined serum levels of the autoantibody in 127 NSCLC patients, 127 age-, gender- and smoking history-matched healthy controls, and 38 patients with pulmonary benign tumors by using a specific enzyme linked immunosorbent assay (ELISA) for the autoantibody...
February 14, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29453518/chimeric-antigen-receptors-with-human-scfvs-preferentially-induce-t-cell-anti-tumor-activity-against-tumors-with-high-b7h6-expression
#8
Albert T Gacerez, Casey K Hua, Margaret E Ackerman, Charles L Sentman
B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. However, mouse single chain variable fragments (scFvs) have the potential to induce host anti-CAR responses that may limit efficacy, so human scFvs specific for B7H6 were selected by yeast surface display...
February 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29452982/reactive-oxygen-species-involvement-in-t-cell-signaling-and-metabolism
#9
REVIEW
Davide G Franchina, Catherine Dostert, Dirk Brenner
T cells are a central component of defenses against pathogens and tumors. Their effector functions are sustained by specific metabolic changes that occur upon activation, and these have been the focus of renewed interest. Energy production inevitably generates unwanted products, namely reactive oxygen species (ROS), which have long been known to trigger cell death. However, there is now evidence that ROS also act as intracellular signaling molecules both in steady-state and upon antigen recognition. The levels and localization of ROS contribute to the redox modeling of effector proteins and transcription factors, influencing the outcome of the T cell response...
February 13, 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29448247/knockdown-of-magea6-activates-amp-activated-protein-kinase-ampk-signaling-to-inhibit-human-renal-cell-carcinoma-cells
#10
Xueting Ye, Jing Xie, Hang Huang, Zhexian Deng
BACKGROUND/AIMS: Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). METHODS: MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29447987/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-soluble-immune-effector-molecules-ii-agents-targeting-interleukins-immunoglobulins-and-complement
#11
REVIEW
Kevin L Winthrop, Xavier Mariette, Jose T Silva, Esther Benamu, Leonard H Calabrese, Alexandre Dumusc, Josef S Smolen, José María Aguado, Mario Fernández-Ruiz
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 12, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29447659/paraneoplastic-pemphigus-in-a-34-year-old
#12
Laura E Melnick, Jenna M Beasley, Randi Kim, Nooshin Brinster, Kristen Lo Sicco
Paraneoplastic Pemphigus (PNP) is a rare and often fatal autoimmune mucocutaneous blistering disease associated with an underlying malignancy. It is thought to be caused by antibodies to tumor antigenscross-reacting with epithelial antigens, specifically desmosomal and hemidesmosomal antigens. There are at least five clinical morphologic variants of PNP, with the earliest and most consistent finding beingsevere stomatitis. Diagnosis of PNP requires direct immunofluorescence of perilesional skin and indirect immunofluorescence...
December 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/29444261/selective-androgen-receptor-modulator-s42-suppresses-prostate-cancer-cell-proliferation
#13
Takako Kawanami, Tomoko Tanaka, Yuriko Hamaguchi, Takashi Nomiyama, Hajime Nawata, Tosihiko Yanase
We previously identified a novel selective androgen receptor modulator (SARM), S42, which does not stimulate prostate growth but has a beneficial effect on lipid metabolism. In the prostate cancer (PC) cell line LNCaP, S42 did not induce androgen receptor (AR) transactivation but antagonized 5α-dihydrotestosterone (DHT)-induced AR activation. Next, we investigated whether S42 suppresses the growth of PC cell lines. Basal growth of LNCaP cells was significantly suppressed by treatment with S42 compared with vehicle, as determined by cell counting and BrdU assays...
February 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29441705/injectable-tough-alginate-cryogels-as-cancer-vaccines
#14
Ting-Yu Shih, Serena O Blacklow, Aileen W Li, Benjamin R Freedman, Sidi Bencherif, Sandeep T Koshy, Max C Darnell, David J Mooney
A covalently crosslinked methacrylated (MA)-alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA-alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked-only cryogels break after injection...
February 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29440708/differential-role-of-fl-bid-and-t-bid-during-verotoxin-1-induced-apoptosis-in-burkitt-s-lymphoma-cells
#15
Justine Debernardi, Emilie Hollville, Marc Lipinski, Joëlle Wiels, Aude Robert
The globotriaosylceramide Gb3 is a glycosphingolipid expressed on a subpopulation of germinal center B lymphocytes which has been recognized as the B cell differentiation antigen CD77. Among tumoral cell types, Gb3/CD77 is strongly expressed in Burkitt's lymphoma (BL) cells as well as other solid tumors including breast, testicular and ovarian carcinomas. One known ligand of Gb3/CD77 is Verotoxin-1 (VT-1), a Shiga toxin produced in specific E. coli strains. Previously, we have reported that in BL cells, VT-1 induces apoptosis via a caspase-dependent and mitochondria-dependent pathway...
February 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29440406/chimeric-antigen-receptor-t-cells-form-nonclassical-and-potent-immune-synapses-driving-rapid-cytotoxicity
#16
A J Davenport, R S Cross, K A Watson, Y Liao, W Shi, H M Prince, P A Beavis, J A Trapani, M H Kershaw, D S Ritchie, P K Darcy, P J Neeson, M R Jenkins
Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29439715/skene-duct%C3%A2-adenocarcinoma-in-a-patient-with-an-elevated-serum-prostate-specific-antigen-level-a-case-report
#17
Sohgo Tsutsumi, Takashi Kawahara, Yusuke Hattori, Taku Mochizuki, Jun-Ichi Teranishi, Kazuhide Makiyama, Yasuhide Miyoshi, Masako Otani, Hiroji Uemura
BACKGROUND: Female urethral carcinoma is a very rare disease that accounts for 0.02% of malignant diseases in female patients. CASE PRESENTATION: A 70-year-old Asian Japanese woman with a urethral tumor was referred to our hospital to undergo further examination. Biopsy specimens showed urethral adenocarcinoma that was positive for prostate-specific antigen. Her serum prostate-specific antigen level before surgery was 34.4 ng/ml. Urethral tumor resection with pelvic lymph node resection was performed...
February 14, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29439670/phase-i-study-of-an-active-immunotherapy-for-asymptomatic-phase-lymphoplasmacytic-lymphoma-with-dna-vaccines-encoding-antigen-chemokine-fusion-study-protocol
#18
Sheeba K Thomas, Soung-Chul Cha, D Lynne Smith, Kun Hwa Kim, Sapna R Parshottam, Sheetal Rao, Michael Popescu, Vincent Y Lee, Sattva S Neelapu, Larry W Kwak
BACKGROUND: There is now a renewed interest in cancer vaccines. Patients responding to immune checkpoint blockade usually bear tumors that are heavily infiltrated by T cells and express a high load of neoantigens, indicating that the immune system is involved in the therapeutic effect of these agents; this finding strongly supports the use of cancer vaccine strategies. Lymphoplasmacytic lymphoma (LPL) is a low grade, incurable disease featuring an abnormal proliferation of Immunoglobulin (Ig)-producing malignant cells...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29438784/novel-antibody-cytokine-fusion-proteins-featuring-granulocyte-colony-stimulating-factor-interleukin-3-and-interleukin-4-as-payloads
#19
Anja Sophie Schmid, Diana Tintor, Dario Neri
Neutrophils can strongly influence disease activity in cancer and in chronic inflammation. Here, we report for the first time the construction and characterization of antibody-fusion proteins featuring granulocyte-colony stimulating factor and interleukin-3 as payloads capable of enhancing neutrophil activity and a novel antibody-interleukin-4 fusion protein with neutrophil inhibitory potential. We used the F8 antibody specific to the alternatively-spliced extra domain A (EDA) of fibronectin as a targeting agent, since the cognate antigen is strongly upregulated in diseases characterized by angiogenesis...
February 10, 2018: Journal of Biotechnology
https://www.readbyqxmd.com/read/29437706/targeting-cyclin-d-cdk4-6-sensitizes-immune-refractory-cancer-by-blocking-the-scp3-nanog-axis
#20
Se Jin Oh, Hanbyoul Cho, Suhyun Kim, Kyung Hee Noh, Kwon-Ho Song, Hyo-Jung Lee, Seon Rang Woo, Suyeon Kim, Chel Hun Choi, Joon-Yong Chung, Stephen M Hewitt, Jae-Hoon Kim, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Hae-Chul Park, Tae Woo Kim
Immune editing caused by anti-tumor immunity drives tumor cells to acquire refractory phenotypes. We demonstrated previously that tumor antigen-specific T cells edit these cells such that they become resistant to CTL killing and enrich NANOGhigh cancer stem cell-like (CSC-like) cells. In the current study, we show that synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, is overexpressed in immune-edited cells and upregulates NANOG by hyperactivating the Cyclin D1-CDK4/6 axis. The SCP3-Cyclin D1-CDK4/6 axis was preserved across various types of human cancer, and correlated negatively with progression-free survival of cervical cancer patients...
February 6, 2018: Cancer Research
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