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Cancer Immunology, Immunotherapy: CII

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https://www.readbyqxmd.com/read/28819703/novel-prostate-cancer-immunotherapy-with-a-dna-encoded-anti-prostate-specific-membrane-antigen-monoclonal-antibody
#1
Kar Muthumani, Liron Marnin, Sagar B Kudchodkar, Alfredo Perales-Puchalt, Hyeree Choi, Sangya Agarwal, Veronica L Scott, Emma L Reuschel, Faraz I Zaidi, Elizabeth K Duperret, Megan C Wise, Kimberly A Kraynyak, Kenneth E Ugen, Niranjan Y Sardesai, J Joseph Kim, David B Weiner
Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life...
August 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28798979/mucosa-associated-invariant-t-cells-infiltrate-hepatic-metastases-in-patients-with-colorectal-carcinoma-but-are-rendered-dysfunctional-within-and-adjacent-to-tumor-microenvironment
#2
Christopher R Shaler, Mauro E Tun-Abraham, Anton I Skaro, Khashayarsha Khazaie, Alexandra J Corbett, Tina Mele, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection...
August 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28795218/atopy-and-prostate-cancer-is-there-a-link-between-circulating-levels-of-ige-and-psa-in-humans
#3
Mieke Van Hemelrijck, Sophia N Karagiannis, Sabine Rohrmann
BACKGROUND: Atopy has been investigated as a potential risk factor for prostate cancer. IgE antibodies may be major players in protective responses against tumours, through engendering antigen presentation and enhancing adaptive immune responses targeted towards a specific allergen, but potentially also against tumour-associated antigens such as prostate-specific antigen (PSA). We therefore cross-sectionally investigated associations between circulating levels of PSA and IgE in the National Health and Nutrition Examination Survey 2005-2006...
August 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28776079/evaluation-of-a-xenogeneic-vascular-endothelial-growth-factor-2-vaccine-in-two-preclinical-metastatic-tumor-models-in-mice
#4
Sofie Denies, Bregje Leyman, Hanne Huysmans, Francis Combes, Séan Mc Cafferty, Laetitia Cicchelero, Marjan Steppe, Joyca De Temmerman, Niek N Sanders
In this study, a xenogeneic DNA vaccine encoding for human vascular endothelial growth factor receptor-2 (hVEGFR-2) was evaluated in two murine tumor models, the B16-F10 melanoma and the EO771 breast carcinoma model. The vaccine was administered by intradermal injection followed by electroporation. The immunogenicity and the biological efficacy of the vaccine were tested in (1) a prophylactic setting, (2) a therapeutic setting, and (3) a therapeutic setting combined with surgical removal of the primary tumor...
August 3, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28770278/an-unbiased-in-vivo-functional-genomics-screening-approach-in-mice-identifies-novel-tumor-cell-based-regulators-of-immune-rejection
#5
Casey W Shuptrine, Reham Ajina, Elana J Fertig, Sandra A Jablonski, H Kim Lyerly, Zachary C Hartman, Louis M Weiner
The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. To address this challenge, we developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immune-competent and immunodeficient mice to select for tumor cell-based genes that regulate in vivo sensitivity to immune attack...
August 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28755091/car-t-cells-targeting-solid-tumors-carcinoembryonic-antigen-cea-proves-to-be-a-safe-target
#6
LETTER
Astrid Holzinger, Hinrich Abken
No abstract text is available yet for this article.
July 28, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28733709/il-4-blockade-alters-the-tumor-microenvironment-and-augments-the-response-to-cancer-immunotherapy-in-a-mouse-model
#7
Shuku-Ei Ito, Hidekazu Shirota, Yuki Kasahara, Ken Saijo, Chikashi Ishioka
Recent findings show that immune cells constitute a large fraction of the tumor microenvironment and that they modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL-4, in particular, is upregulated. Thus, we tested whether IL-4 neutralization would affect tumor immunity. Current results demonstrate that the administration of a neutralizing antibody against IL-4 enhances anti-tumor immunity and delays tumor progression. IL-4 blockade also alters inflammation in the tumor microenvironment, reducing the generation of both immunosuppressive M2 macrophages and myeloid-derived suppressor cells, and enhancing tumor-specific cytotoxic T lymphocytes...
July 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#8
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28712033/oncolytic-immunotherapy-unlocking-the-potential-of-viruses-to-help-target-cancer
#9
REVIEW
Omid Hamid, Brianna Hoffner, Eduard Gasal, Jenny Hong, Richard D Carvajal
Oncolytic immunotherapy is a research area of cancer immunotherapy investigating the use of modified viruses to target cancer cells. A variety of different viral backbones (e.g., adenovirus, reovirus) with a diverse range of genetic modifications are currently being investigated for the treatment of a variety of cancers. The oncolytic virus that has advanced the furthest in clinical development is talimogene laherparepvec, a recombinant HSV-1 virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF)...
July 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28710511/cerebellar-degeneration-related-proteins-2-and-2-like-are-present-in-ovarian-cancer-in-patients-with-and-without-yo-antibodies
#10
Margrethe Raspotnig, Mette Haugen, Maria Thorsteinsdottir, Ingunn Stefansson, Helga B Salvesen, Anette Storstein, Christian A Vedeler
BACKGROUND: Cerebellar degeneration-related protein 2 (CDR2) has been presumed to be the main antigen for the onconeural antibody Yo, which is strongly associated with ovarian cancer and paraneoplastic cerebellar degeneration (PCD). Recent data show that Yo antibodies also target the CDR2-like protein (CDR2L). We, therefore, examined the expression of CDR2 and CDR2L in ovarian cancer tissue from patients with and without Yo antibodies and from various other cancerous and normal human tissues...
July 14, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28707078/ctla-4-expression-in-the-non-small-cell-lung-cancer-patient-tumor-microenvironment-diverging-prognostic-impact-in-primary-tumors-and-lymph-node-metastases
#11
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee, Elin Richardsen, Sigurd M Hald, Sigve Andersen, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I-IIIA NSCLC. Expression of CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional metastatic lymph nodes...
July 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28695228/-tumor-immunology-meets-oncology-timo-xii-april-28th-30th-2016-halle-saale-germany
#12
Barbara Seliger
No abstract text is available yet for this article.
July 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28689360/regulatory-myeloid-cells-an-underexplored-continent-in-b-cell-lymphomas
#13
REVIEW
Mikael Roussel, Jonathan M Irish, Cedric Menard, Faustine Lhomme, Karin Tarte, Thierry Fest
In lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors. However, the M1/M2 nomenclature is now deprecated and the clinical impact of this phenotype remains controversial. Across cancer types, myeloid cells are primarily thought to function as immune suppressors during tumor initiation and maintenance, but the biological mechanisms behind the myeloid signatures are still poorly understood in germinal center B-cell lymphomas...
July 8, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28688082/circulating-myeloid-derived-suppressor-cells-increase-in-patients-undergoing-neo-adjuvant-chemotherapy-for-breast-cancer
#14
Robert Wesolowski, Megan C Duggan, Andrew Stiff, Joseph Markowitz, Prashant Trikha, Kala M Levine, Lynn Schoenfield, Mahmoud Abdel-Rasoul, Rachel Layman, Bhuvaneswari Ramaswamy, Erin R Macrae, Maryam B Lustberg, Raquel E Reinbolt, Ewa Mrozek, John C Byrd, Michael A Caligiuri, Thomas A Mace, William E Carson Iii
This study sought to evaluate whether myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic complete response (pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and 1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24 patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+, respectively...
July 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28674756/immune-biomarkers-for-chronic-inflammation-related-complications-in-non-cancerous-and-cancerous-diseases
#15
REVIEW
Yaron Meirow, Michal Baniyash
Chronic inflammation arising in a diverse range of non-cancerous and cancerous diseases, dysregulates immunity and exposes patients to a variety of complications. These include immunosuppression, tissue damage, cardiovascular diseases and more. In cancer, chronic inflammation and related immunosuppression can directly support tumor growth and dramatically reduce the efficacies of traditional treatments, as well as novel immune-based therapies, which require a functional immune system. Nowadays, none of the immune biomarkers, regularly used by clinicians can sense a developing chronic inflammation, thus complications can only be detected upon their appearance...
July 3, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28660319/the-clinical-efficacy-of-first-generation-carcinoembryonic-antigen-ceacam5-specific-car-t-cells-is-limited-by-poor-persistence-and-transient-pre-conditioning-dependent-respiratory-toxicity
#16
Fiona C Thistlethwaite, David E Gilham, Ryan D Guest, Dominic G Rothwell, Manon Pillai, Deborah J Burt, Andrea J Byatte, Natalia Kirillova, Juan W Valle, Surinder K Sharma, Kerry A Chester, Nigel B Westwood, Sarah E R Halford, Stephen Nabarro, Susan Wan, Eric Austin, Robert E Hawkins
The primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5(+) malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5(+)-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion. Patients in cohort 4 received increased intensity pre-conditioning (cyclophosphamide and fludarabine), systemic IL2 support and CAR T cells...
June 28, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28634816/critical-biological-parameters-modulate-affinity-as-a-determinant-of-function-in-t-cell-receptor-gene-modified-t-cells
#17
Timothy T Spear, Yuan Wang, Kendra C Foley, David C Murray, Gina M Scurti, Patricia E Simms, Elizabeth Garrett-Mayer, Lance M Hellman, Brian M Baker, Michael I Nishimura
T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28634815/autoimmune-diabetes-induced-by-pd-1-inhibitor-retrospective-analysis-and-pathogenesis-a-case-report-and-literature-review
#18
Marie-Léa Gauci, Pauline Laly, Tiphaine Vidal-Trecan, Barouyr Baroudjian, Jérémy Gottlieb, Nika Madjlessi-Ezra, Laetitia Da Meda, Isabelle Madelaine-Chambrin, Martine Bagot, Nicole Basset-Seguin, Cécile Pages, Samia Mourah, Philippe Boudou, Céleste Lebbé, Jean-François Gautier
Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with nivolumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28623459/blockade-of-cd112r-and-tigit-signaling-sensitizes-human-natural-killer-cell-functions
#19
Feng Xu, Alexander Sunderland, Yue Zhou, Richard D Schulick, Barish H Edil, Yuwen Zhu
Trastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. We found that all PVR-like receptors are expressed on human NK cells, and only TIGIT is preferentially expressed on the CD16+ NK cell subset. Disrupting the interactions of PVR-like receptors with their ligands on cancer cells regulates NK cell activity...
June 16, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28612140/a-phase-ii-study-of-ipilimumab-plus-temozolomide-in-patients-with-metastatic-melanoma
#20
Sapna P Patel, Dae Won Kim, Roland L Bassett, Suzanne Cain, Edwina Washington, Wen-Jen Hwu, Kevin B Kim, Nicholas E Papadopoulos, Jade Homsi, Patrick Hwu, Agop Y Bedikian
Checkpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest that temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with ipilimumab...
June 13, 2017: Cancer Immunology, Immunotherapy: CII
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