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Tumor specific antigens

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https://www.readbyqxmd.com/read/27926855/temporally-programmed-cd8%C3%AE-dc-activation-enhances-combination-cancer-immunotherapy
#1
Alice Tzeng, Monique J Kauke, Eric F Zhu, Kelly D Moynihan, Cary F Opel, Nicole J Yang, Naveen Mehta, Ryan L Kelly, Gregory L Szeto, Willem W Overwijk, Darrell J Irvine, K Dane Wittrup
Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α(+) dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27924731/improved-immunogenicity-against-a-her2-neu-derived-peptide-by-employment-of-a-pan-hla-dr-binding-epitope-and-cpg-in-a-balb-c-mice-model
#2
Sahar Tahaghoghi-Hajghorbani, Jalil Tavakkol-Afshari, Mahmoud Reza Jaafari, Haniyeh Ghaffari-Nazari, Elham Masoumi, Seyed Amir Jalali
BACKGROUND: An efficient strategy to improve the immunogenicity of peptide vaccines is the use of a synthetic peptide containing cytotoxic T-lymphocyte (CTL) epitopes with T-helper (Th) inducing-epitopes. OBJECTIVE: Our purpose was to determine the use of human epidermal growth factor receptor-2 (Her2/neu)-specific CTL epitopes plus the pan HLA DR-binding epitope (PADRE) and CpG oligodeoxynucleotides (ODNs) to induce antitumor effects in vaccinated mice. METHOD: Female BALB/c mice were immunized with subcutaneously the different vaccines...
December 6, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27924159/in-vitro-and-in-vivo-evaluation-of-89-zr-ds-8273a-as-a-theranostic-for-anti-death-receptor-5-therapy
#3
Ingrid J G Burvenich, Fook-Thean Lee, Nancy Guo, Hui K Gan, Angela Rigopoulos, Adam C Parslow, Graeme J O'Keefe, Sylvia J Gong, Henri Tochon-Danguy, Stacey E Rudd, Paul S Donnelly, Masakatsu Kotsuma, Toshiaki Ohtsuka, Giorgio Senaldi, Andrew M Scott
Background: DS-8273a, an anti-human death receptor 5 (DR5) agonistic antibody, has cytotoxic activity against human cancer cells and induces apoptosis after specific binding to DR5. DS-8273a is currently being used in clinical Phase I trials. This study evaluated the molecular imaging of DR5 expression in vivo in mouse tumor models using SPECT/CT and PET/MRI, as a tool for drug development and trial design. Methods: DS-8273a was radiolabeled with indium-111 and zirconium-89. Radiochemical purity, immunoreactivity, antigen binding affinity and serum stability were assessed in vitro...
2016: Theranostics
https://www.readbyqxmd.com/read/27924074/optimized-t-cell-receptor-mimic-tcrm-chimeric-antigen-receptor-t-cells-directed-towards-the-intracellular-wilms-tumor-1-antigen
#4
S Rafiq, T J Purdon, A F Daniyan, M Koneru, T Dao, C Liu, D A Scheinberg, R J Brentjens
CD19-directed chimeric antigen receptor (CAR) T-cells are clinically effective in a limited set of leukemia patients. However, CAR T-cell therapy thus far has been largely restricted to targeting extracellular tumor-associated antigens (TAA). Herein, we report a T-cell receptor-mimic (TCRm) CAR, termed WT1-28z, that is reactive to a peptide portion of the intracellular onco-protein Wilms Tumor 1(WT1), as it is expressed on the surface of the tumor cell in the context of HLA-A*02:01. T-cells modified to express WT1-28z specifically targeted and lysed HLA-A*02:01+ WT1+ tumors and enhanced survival of mice engrafted with HLA-A*02:01+, WT1+ leukemia or ovarian tumors...
December 7, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27922937/repurposing-ospemifene-for-potentiating-an-antigen-specific-immune-response
#5
Chiao-Jung Kao, Gregory T Wurz, Yi-Chen Lin, Daniel P Vang, Brian Phong, Michael W DeGregorio
OBJECTIVE: Ospemifene, an estrogen receptor agonist/antagonist approved for the treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine. METHODS: Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T-cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo...
December 5, 2016: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/27922687/immature-myeloid-derived-suppressor-cells-a-bridge-between-inflammation-and-cancer-review
#6
Caterina Musolino, Alessandro Allegra, Govanni Pioggia, Sebastiano Gangemi
Chronic inflammation is considered to be one of the hallmarks of tumor initiation and progression. Changes occurring in the microenvironment of progressing tumors resemble the process of chronic inflammation, which begins with ischemia followed by interstitial and cellular edema, appearance of immune cells, growth of blood vessels and tissue repair, and development of inflammatory infiltrates. Moreover, long‑term production and accumulation of inflammatory factors lead to local and systemic immunosuppression associated with cancer progression...
December 5, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922627/blood-based-and-urinary-prostate-cancer-biomarkers-a-review-and-comparison-of-novel-biomarkers-for-detection-and-treatment-decisions
#7
REVIEW
R J Hendriks, I M van Oort, J A Schalken
BACKGROUND: The diagnosis of prostate cancer (PCa) is currently based on serum PSA testing and/or abnormal digital rectal examination and histopathologic evaluation of prostate biopsies. The main drawback of PSA testing is the lack of specificity for PCa. To improve early detection of PCa more specific biomarkers are needed. In the past few years, many new promising biomarkers have been identified; however, to date, only a few have reached clinical practice. METHODS: In this review, we discuss new blood-based and urinary biomarker models that are promising for usage in PCa detection, follow-up and treatment decision-making...
December 6, 2016: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/27921025/prostate-specific-antigen-rising-in-iranian-men-in-correlation-with-body-mass-index-fasting-blood-sugar-and-blood-lipid-profile
#8
Davood Arab, Arash Ardestani Zadeh, Majid Mirmohammadkhani, Azadeh Beiglarzadeh
BACKGROUND: Prostate-specific antigen (PSA) is a serine protease that is secreted by prostate cells and it is useful as a tumor marker for prostate cancer. OBJECTIVES: In this study, the relationship between some of metabolic factors and serum PSA level was investigated. MATERIALS AND METHODS: In this cross-sectional study, patients with urinary symptoms or for screening of the prostate cancer (after 50 years of age or 40 years with a family history of prostate cancer), were evaluated...
October 2016: Journal of Nephropathology
https://www.readbyqxmd.com/read/27920218/a-molecular-basis-for-the-presentation-of-phosphorylated-peptides-by-hla-b-antigens
#9
Adán Alpízar, Fabio Marino, Antonio Ramos-Fernández, Manuel Lombardía, Anita Jeko, Florencio Pazos, Alberto Paradela, César Santiago, Albert J R Heck, Miguel Marcilla
As aberrant protein phosphorylation is a hallmark of tumor cells, the display of tumor-specific phosphopeptides by Human Leukocyte Antigen (HLA) class I molecules can be exploited in the treatment of cancer by T-cell-based immunotherapy. Yet, the characterization and prediction of HLA-I phospholigands is challenging as the molecular determinants of the presentation of such post-translationally modified peptides are not fully understood. Here, we employed a peptidomic workflow to identify 256 unique phosphorylated ligands associated with HLA-B*40, -B*27, -B*39 or -B*07...
December 5, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27919982/clinical-significance-of-the-apparent-diffusion-coefficient-ratio-in-prostate-cancer-treatment-with-intensity-modulated-radiotherapy
#10
Hiroko Yamaguchi, Masatoshi Hori, Osamu Suzuki, Yuji Seo, Fumiaki Isohashi, Yasuo Yoshioka, Iori Sumida, Motohide Uemura, Kazutoshi Fujita, Akira Nagahara, Takeshi Ujike, Atsunari Kawashima, Norio Nonomura, Noriyuki Tomiyama, Kazuhiko Ogawa
AIM: We aimed to investigate the correlation between biochemical recurrence (BCR) and the pretreatment apparent diffusion coefficient (ADC) ratio of tumor to normal prostate tissue in patients with prostate cancer who underwent intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS: Retrospective analyses were performed for 101 patients diagnosed with localized prostate cancer who underwent IMRT at a dose of 70-78 Gy to the prostate gland and medial part of the seminal vesicles...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#11
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27917441/size-selective-harvesting-of-extracellular-vesicles-for-strategic-analyses-towards-tumor-diagnoses
#12
Chihiro Manri, Takahide Yokoi, Hirokazu Nishida
Extracellular vesicles (EV), typified by exosomes or microvesicles, are expected to be effective diagnostic markers for cancers. The sizes of the vesicles range from 20 to 1000 nm, but the size-dependent variations of the contents of EVs are still poorly understood. We succeeded in the size-selective harvesting of the vesicles by utilizing the molecular weight-dependent characteristics of a variety of polyethylene glycols (PEG) as precipitating reagents and analyzed the antigens displayed on the surfaces of the vesicles and the miRNAs included in the vesicles from each size group...
December 5, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27916435/analytical-validation-of-androgen-receptor-splice-variant-7-detection-in-a-clinical-laboratory-improvement-amendments-clia-laboratory-setting
#13
Parvez M Lokhandwala, Stacy L Riel, Lisa Haley, Changxue Lu, Yan Chen, John Silberstein, Yezi Zhu, Gang Zheng, Ming-Tseh Lin, Christopher D Gocke, Alan W Partin, Emmanuel S Antonarakis, Jun Luo, James R Eshleman
Patients with castration-resistant prostate cancer (CRPC) often are treated with drugs that target the androgen receptor (AR) ligand-binding domain. Constitutively active AR splice variant 7 (AR-V7) lacks the ligand-binding domain and, if detected in circulating tumor cells, may be associated with resistance to these agents. We validated an AR-V7 assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Circulating tumor cells were isolated, and mRNA was reverse-transcribed into cDNA...
December 1, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27916138/alcohol-exposure-differentially-effects-anti-tumor-immunity-in-females-by-altering-dendritic-cell-function
#14
Matthew G Thompson, Flor Navarro, Lennox Chitsike, Luis Ramirez, Elizabeth J Kovacs, Stephanie K Watkins
Dendritic cells (DCs) are a critical component of anti-tumor immunity due to their ability to induce a robust immune response to antigen (Ag). Alcohol was previously shown to reduce DC ability to present foreign Ag and promote pro-inflammatory responses in situations of infection and trauma. However the impact of alcohol exposure on generation of an anti-tumor response, especially in the context of generation of an immune vaccine has not been examined. In the clinic, DC vaccines are typically generated from autologous blood, therefore prior exposure to substances such as alcohol may be a critical factor to consider regarding the effectiveness in generating an immune response...
December 2016: Alcohol
https://www.readbyqxmd.com/read/27916120/development-and-statistical-assessment-of-a-paper-based-immunoassay-for-detection-of-tumor-markers
#15
Thiago Mazzu-Nascimento, Giorgio Gianini Morbioli, Luis Aparecido Milan, Fabiana Cristina Donofrio, Carlos Alberto Mestriner, Emanuel Carrilho
Paper-based assays are an attractive low-cost option for clinical chemistry testing, due to characteristics such as short time of analysis, low consumption of samples and reagents, and high portability of assays. However, little attention has been given to the evaluation of the performance of these simple tests, which should include the use of a statistical approach to define the choice of best cut-off value for the test. The choice of the cut-off value impacts on the sensitivity and specificity of the bioassay...
January 15, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27915475/how-precisely-can-prostate-cancer-be-managed
#16
REVIEW
Liyan Zhuang, Matthew T Johnson
Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2- ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27913835/preventive-dna-vaccination-against-cea-expressing-tumors-with-anti-idiotypic-scfv6-c4-dna-in-cea-expressing-transgenic-mice
#17
Priscila M A Denapoli, Bianca F Zanetti, Adara A Dos Santos, Jane Z de Moraes, Sang W Han
Carcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682...
December 2, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27913506/checkpoint-inhibition-and-cellular-immunotherapy-in-lymphoma
#18
Premal Lulla, Helen E Heslop
Hodgkin and non-Hodgkin lymphoma are both good targets for immunotherapy, as they are accessible to antibodies and cell-based immunotherapy, express costimulatory molecules, and express lineage-restricted, viral, and unique tumor antigens. Blockade of the programmed-death 1 (PD-1) immune checkpoint has produced very encouraging response rates in patients with Hodgkin lymphoma, whereas adoptive transfer of Epstein-Barr Virus (EBV)-specific T cells has shown clinical activity in patients with posttransplant lymphoma and other EBV-associated lymphomas...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911459/evaluation-of-bone-metastases-by-18f-choline-pet-ct-in-a-patient-with-castration-resistant-prostate-cancer-treated-with-radium-223
#19
Piera Scalzi, Cinzia Baiocco, Sabrina Genovese, Antonella Trevisan, Zuzana Sirotova, Carlo Poti
BACKGROUND: To date, bone metastases remain the main cause of morbidity and mortality in patients with metastatic castration-resistant prostate cancer (mCRPC). Therefore, the combination of accurate early detection of bony disease and effective treatment of these lesions is crucial in the management of mCRPC patients, but clinical trials specifically designed to test novel approaches are currently lacking. CASE DESCRIPTION: This report describes the case of a 74-year-old male with bone mCRPC and symptomatic and biochemical progression, who underwent radium-223 therapy, following previous treatment failure...
December 2, 2016: Urologia
https://www.readbyqxmd.com/read/27910914/in-vivo-stepwise-immunomodulation-using-chitosan-nanoparticles-as-a-platform-nanotechnology-for-cancer-immunotherapy
#20
Hee Dong Han, Yeongseon Byeon, Jong-Hwa Jang, Hat Nim Jeon, Ga Hee Kim, Min Gi Kim, Chan-Gi Pack, Tae Heung Kang, In Duk Jung, Yong Taik Lim, Young Joo Lee, Jeong-Won Lee, Byung Cheol Shin, Hyung Jun Ahn, Anil K Sood, Yeong-Min Park
Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes...
December 2, 2016: Scientific Reports
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