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Tumor specific antigens

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https://www.readbyqxmd.com/read/29667553/car-t-cell-therapy-a-new-era-in-cancer-immunotherapy
#1
Miliotou N Androulla, Papadopoulou C Lefkothea
BACKGROUND: Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient's immune system. METHODS: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient's autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient...
April 17, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29667346/in-situ-vaccination-harvesting-low-hanging-fruit-on-the-cancer-immunotherapy-tree
#2
REVIEW
Mee Rie Sheen, Steven Fiering
After 100 years of debate, it is clear that cancer is recognized by the immune system and this has generated immense interest in cancer immunotherapy. The systemic nature of the immune system gives immunotherapy the ability to treat metastatic disease, which currently requires chemotherapy that frequently fails. Like chemotherapy, most immunotherapy is systemically applied in an effort to generate systemic antitumor immune response. However, local administration of immunostimulatory reagents into a recognized tumor by in situ vaccination (ISV) can also generate systemic antitumor immunity to fight metastatic disease...
April 18, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29666835/aptamers-and-apple-pies-a-mini-review-of-psma-aptamers-and-lessons-from-donald-s-coffey
#3
REVIEW
Shawn E Lupold
This mini-review article is part of a special issue dedicated to Donald S. Coffey, a pioneer translational research scientist, exemplary mentor, and leader in urologic and urologic oncology research. This article first briefly reflects on life and scientific lessons from Don Coffey. It then reviews the development of two prostate cancer targeting RNA aptamers, xPSM-A9 and xPSM-A10, through in vitro selection for aptamers that bind to the extracellular domain of the Prostate Specific Membrane Antigen (PSMA)...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29665944/-current-status-and-challenges-of-car-t-immunotherapy-in-hematologic-malignancies-review
#4
Xin Cheng, Ya-Jie Wang, Shuai Feng, Ya-Yun Wu, Tong-Hua Yang, Xun Lai
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29663383/nanoparticle-based-targeted-cancer-strategies-for-non-invasive-prostate-cancer-intervention
#5
REVIEW
Nicholas H Farina, Areg Zingiryan, Michael A Vrolijk, Scott D Perrapato, Steven Ades, Gary S Stein, Jane B Lian, Christopher C Landry
Prostate cancer is screened by testing circulating levels of the prostate-specific antigen (PSA) biomarker, monitoring changes over time, or a digital rectal exam. Abnormal results often lead to prostate biopsy. Prostate cancer positive patients are stratified into very low-risk, low-risk, intermediate-risk, and high-risk, based on clinical classification parameters, to assess therapy options. However, there remains a gap in our knowledge and a compelling need for improved risk stratification to inform clinical decisions and reduce both over-diagnosis and over-treatment...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29662647/characterization-of-increasing-stages-of-invasiveness-identifies-stromal-cancer-cell-crosstalk-in-rat-models-of-mesothelioma
#6
Joëlle S Nader, Jérôme Abadie, Sophie Deshayes, Alice Boissard, Stéphanie Blandin, Christophe Blanquart, Nicolas Boisgerault, Olivier Coqueret, Catherine Guette, Marc Grégoire, Daniel L Pouliquen
Sarcomatoid mesothelioma (SM) is a devastating cancer associated with one of the poorest outcome. Therefore, representative preclinical models reproducing different tumor microenvironments (TME) observed in patients would open up new prospects for the identification of markers and evaluation of innovative therapies. Histological analyses of four original models of rat SM revealed their increasing infiltrative and metastatic potential were associated with differences in Ki67 index, blood-vessel density, and T-lymphocyte and macrophage infiltration...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661963/obesity-suppresses-tumor-attributable-psa-affecting-risk-categorization
#7
Ken Chow, Stefano Mangiola, Jaideep Vazirani, Justin S Peters, Anthony J Costello, Christopher M Hovens, Niall M Corcoran
Obesity is linked with more aggressive prostate cancer and higher rates of disease recurrence post treatment. It is unclear if this is due to specific tumor-promoting effects of obesity or diagnostic bias. Patients undergoing prostatectomy were categorized according to their body mass index (BMI). Expected prostate-specific antigen (PSA) levels were calculated for each patient based on tumor characteristics. The effect of obesity on the accuracy of pre-treatment risk categorization was determined, and mediation analysis was used to identify the contribution of biologic vs non-biologic mechanisms to the observed increased risk of biochemical recurrence...
May 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29661587/medium-term-follow-up-of-vascular-targeted-photodynamic-therapy-of-localized-prostate-cancer-using-tookad-soluble-wst-11-phase-ii-trials
#8
A Noweski, A Roosen, S Lebdai, E Barret, M Emberton, F Benzaghou, M Apfelbeck, B Gaillac, C Gratzke, C Stief, A R Azzouzi
BACKGROUND AND OBJECTIVE: To assess the medium-term tumor control in patients with localized prostate cancer (PCa) treated with vascular-targeted photodynamic (VTP) therapy with TOOKAD Soluble WST11 (VTP) and to assess the medium-term tolerability of the treatment. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: During the clinical phase II studies, 68 patients were treated with VTP under optimal treatment conditions (WST11 at 4mg/kg, light energy at 200J/cm, and a light density index ≥1) and have been included in a 3...
April 13, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29660918/contrast-enhanced-ultrasound-ceus-with-mri-image-fusion-for-monitoring-focal-therapy-of-prostate-cancer-with-high-intensity-focused-ultrasound-hifu-1
#9
M Apfelbeck, D-A Clevert, J Ricke, C Stief, B Schlenker
INTRODUCTION: Reduced acceptance of radical prostatectomy in patients with low risk or intermediate risk prostate cancer has significantly changed treatment strategies in prostate cancer (PCa) during the last years. Focal therapy of the prostate with high intensity focused ultrasound (HIFU) is an organ-preserving treatment for prostate cancer with less impairment of health-related quality of life. Follow-up after HIFU therapy by imaging modalities remains a major problem as eg. MRI performs poorly...
April 7, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29660844/moray-micro-forceps-biopsy-improves-the-diagnosis-of-specific-pancreatic-cysts
#10
M Lisa Zhang, Ronald N Arpin, William R Brugge, David G Forcione, Omer Basar, Martha B Pitman
BACKGROUND: Making a specific diagnosis of pancreatic cysts preoperatively is difficult. The new disposable Moray micro forceps biopsy (MFB) device allows tissue sampling from the pancreatic cyst wall/septum and aims to improve diagnosis. This study compares the diagnostic performance of the MFB with the current conventional analysis of pancreatic cyst fluid (PCF). METHODS: A total of 48 patients sampled with MFB were identified. Cysts were classified as mucinous on PCF based on extracellular mucin/mucinous epithelium, carcinoembryonic antigen (CEA) levels ≥192 ng/mL, or KRAS/GNAS mutation...
April 16, 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29659051/psa-alpha-2-macroglobulin-complex-is-enzymatically-active-in-the-serum-of-patients-with-advanced-prostate-cancer-and-can-degrade-circulating-peptide-hormones
#11
Maya B Kostova, William Nathaniel Brennen, David Lopez, Lizamma Anthony, Hao Wang, Elizabeth Platz, Samuel R Denmeade
BACKGROUND: Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured...
April 16, 2018: Prostate
https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#12
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29656066/the-clinical-course-of-patients-with-psa%C3%A2-100-ng-ml-insight-into-a-potential-population-for-targeted-psa-screening
#13
Andrew K Leung, Lee Hugar, Dattatraya Patil, Lisa Wong, Bradley Carthon, Kenneth Carney, George Birdsong, Kelvin A Moses, Viraj A Master
OBJECTIVE: To characterize men presenting to a tertiary care safety-net hospital with prostate-specific antigen (PSA) values ≥100 ng/mL and identify a potential population for targeted PSA screening. METHODS: Retrospective review of 100 randomly selected patients out of 204 total who presented to Grady Memorial Hospital from 2004-2011 with initial PSA≥100 ng/mL was performed. Demographics, disease characteristics, and survival status were obtained via the Tumor Registry and a combination of electronic medical records and older paper charts, with missing data from paper charts excluded on analyses...
April 12, 2018: Urology
https://www.readbyqxmd.com/read/29656061/hypoxia-inducible-bidirectional-shrna-expression-vector-delivery-using-pei-chitosan-tba-copolymers-for-colorectal-cancer-gene-therapy
#14
Bita Javan, Fatemeh Atyabi, Majid Shahbazi
AIMS: This investigation was conducted to construct a hypoxia/colorectal dual-specific bidirectional short hairpin RNA (shRNA) expression vector and to transfect it into the colon cancer cell line HT-29 with PEI/chitosan-TBA nanoparticles for the simultaneous knock down of β-catenin and Bcl-2 under hypoxia. MAIN METHODS: To construct a pRNA-bipHRE-CEA vector, the carcinoma embryonic antigen (CEA) promoter designed in two directions and the vascular endothelial growth factor (VEGF) enhancer were inserted between two promoters for hypoxic cancer specific gene expression...
April 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29655611/development-of-a-ga-68-labeled-pet-tracer-with-short-linker-for-prostate-specific-membrane-antigen-psma-targeting
#15
Sung-Hyun Moon, Mee Kyung Hong, Young Ju Kim, Yun-Sang Lee, Dong Soo Lee, June-Key Chung, Jae Min Jeong
Glu-Urea-Lys (GUL) derivatives have been reported as prostate-specific membrane antigen (PSMA) agent. We developed derivatives of GUL conjugated with NOTA or DOTA via a thiourea linker and tested their feasibility as PSMA imaging agents after labeling with 68 Ga. NOTA-GUL and DOTA-GUL were synthesized and labeled with 68 Ga using generator-eluted 68 GaCl3 in 0.1 M HCl in the presence of 1 M NaOAc at pH 5.5. The stabilities of 68 Ga-labeled compounds in human serum were tested at 37.5 °C. A competitive binding assay was performed using the PSMA-positive prostate cancer cell line 22Rv1 and [125 I]MIP-1072 (PSMA-specific binding agent) as a tracer...
April 5, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29651744/prospects-of-chimeric-antigen-receptor-t-cell-therapy-in-ovarian-cancer
#16
REVIEW
Vishal Jindal, Ena Arora, Sorab Gupta, Amos Lal, Muhammad Masab, Rashmika Potdar
Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Immunotherapy provides a promising and novel treatment option for ovarian cancer. Recently, chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematological tumors and current research is going on in various solid tumors like ovarian cancer. CAR T cells are genetically engineered T cells with major histocompatibility complex-independent, tumor-specific, immune-mediated cytolytic actions against cancer cells...
April 12, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29651565/synthesis-and-preclinical-evaluation-of-novel-18-f-labeled-glu-urea-glu-based-psma-inhibitors-for-prostate-cancer-imaging-a-comparison-with-18-f-dcfpyl-and-18-f-psma-1007
#17
Stephanie Robu, Alexander Schmidt, Matthias Eiber, Margret Schottelius, Thomas Günther, Behrooz Hooshyar Yousefi, Markus Schwaiger, Hans-Jürgen Wester
BACKGROUND: Due to its high and consistent expression in prostate cancer (PCa), the prostate-specific membrane antigen (PSMA) represents an ideal target for molecular imaging and targeted therapy using highly specific radiolabeled PSMA ligands. To address the continuously growing clinical demand for 18 F-labeled PSMA-probes, we developed two novel Glu-urea-Glu-(EuE)-based inhibitors, EuE-k-18 F-FBOA (1) and EuE-k-β-a-18 F-FPyl (2), both with optimized linker structure and different 18 F-labeled aromatic moieties...
April 12, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/29649590/effective-intracellular-delivery-and-th1-immune-response-induced-by-ovalbumin-loaded-in-ph-responsive-polyphosphazene-polymersomes
#18
Menghua Gao, Yan Peng, Liming Jiang, Liyan Qiu
A polymersome system for delivering protein antigen ovalbumin (OVA) based on amphiphilic polyphosphazene grafting with N,N-diisopropylethylenediamine (DPA) and poly(ethylene glycol) (PEG) groups (poly[(DPA)m (PEG)n phosphazene], PEDP) was designed and constructed. The 200~240nm-size OVA-loaded polymersomes displayed high stability at physiological pH, slow internalization through clathrin-mediated endocytosis pathway, and then a pH-triggered sustained OVA release in acidic environment, leading to extensive antigen access to cytosol...
April 9, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29645087/a-humanized-tcr-retaining-authentic-specificity-and-affinity-conferred-potent-anti-tumor-cytotoxicity
#19
Lin Chen, Ye Tian, Kai Zhan, Anan Chen, Zhiming Weng, Jiao Huang, Yanyan Li, Yongjie Sun, Hongjun Zheng, Yi Li
The affinity of T cell receptor (TCR) determines the efficacy of TCR based immunotherapy. By using human leukocyte antigen (HLA)-A*02 transgenic mice, a TCR was generated previously specific for human tumor testis antigen peptide MAGE-A3112-120 (KVAELVHFL) HLA-A*02 complex. We developed an approach to humanize the murine TCR by replacing the mouse framework with sequences of folding optimized human TCR variable domains for retaining binding affinity. The resultant humanized TCR exhibited higher affinity and conferred better anti-tumor activity than its parent murine MAGE-A3 TCR (SRm1)...
April 12, 2018: Immunology
https://www.readbyqxmd.com/read/29644213/immunotherapy-plus-cryotherapy-potential-augmented-abscopal-effect-for-advanced-cancers
#20
REVIEW
Joe Abdo, David L Cornell, Sumeet K Mittal, Devendra K Agrawal
Since the 1920s the gold standard for treating cancer has been surgery, which is typically preceded or followed with chemotherapy and/or radiation, a process that perhaps contributes to the destruction of a patient's immune defense system. Cryosurgery ablation of a solid tumor is mechanistically similar to a vaccination where hundreds of unique antigens from a heterogeneous population of tumor cells derived from the invading cancer are released. However, releasing tumor-derived self-antigens into circulation may not be sufficient enough to overcome the checkpoint escape mechanisms some cancers have evolved to avoid immune responses...
2018: Frontiers in Oncology
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