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anti pd 1 melanoma

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https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#1
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29764498/talimogene-laherparepvec-combined-with-anti-pd-1-based-immunotherapy-for-unresectable-stage-iii-iv-melanoma-a-case-series
#2
Lillian Sun, Pauline Funchain, Jung Min Song, Patricia Rayman, Charles Tannenbaum, Jennifer Ko, Michael Mcnamara, C Marcela Diaz-Montero, Brian Gastman
BACKGROUND: Talimogene Laherparepvec (T-VEC) is an oncolytic virus approved as an intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action for T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining checkpoint inhibitor therapy with T-VEC injection can lead to improved response rates for stage IIIB-IV melanoma patients. METHODS: We reviewed 10 consecutive cases of stage IIIC to stage IVM1b melanoma patients that received T-VEC plus checkpoint inhibitor(s) therapy (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June 2016 and August 2017 at the Cleveland Clinic with a median follow-up of 7 months (range: 4 to 13 months)...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29760383/outlier-response-to-anti-pd1-in-uveal-melanoma-reveals-germline-mbd4-mutations-in-hypermutated-tumors
#3
Manuel Rodrigues, Lenha Mobuchon, Alexandre Houy, Alice Fiévet, Sophie Gardrat, Raymond L Barnhill, Tatiana Popova, Vincent Servois, Aurore Rampanou, Aurore Mouton, Stéphane Dayot, Virginie Raynal, Michèle Galut, Marc Putterman, Sarah Tick, Nathalie Cassoux, Sergio Roman-Roman, François-Clément Bidard, Olivier Lantz, Pascale Mariani, Sophie Piperno-Neumann, Marc-Henri Stern
Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactivation in the tumor. We identify additional tumors in The Cancer Genome Atlas (TCGA) cohorts with similar hypermutator profiles in patients carrying germline deleterious MBD4 mutations and somatic loss of heterozygosity...
May 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29750753/immune-checkpoint-inhibitor-anti-ctla-4-anti-pd-1-therapy-alone-versus-immune-checkpoint-inhibitor-anti-ctla-4-anti-pd-1-therapy-in-combination-with-anti-rankl-denosumuab-in-malignant-melanoma-a-retrospective-analysis-at-a-tertiary-care-center
#4
Muhammad Z Afzal, Keisuke Shirai
Denosumab is a monoclonal antibody against RANK ligand with a role in the prevention of skeletal-related events and is also known to possess antitumor properties. In this retrospective review, we aim to evaluate the synergist effect of a combination therapy with immune checkpoint inhibitors and denosumab in malignant melanoma patients. Patients of 18 years of age or older with a diagnosis of malignant melanoma who have received immune checkpoint inhibitors and denosumab between June 2015 and May 2017 were divided into two cohorts: cohort A (immune checkpoint inhibitors only) and cohort B (immune checkpoint inhibitors and denosumab)...
May 10, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29746296/pd-1-contributes-to-the-establishment-and-maintenance-of-hiv-1-latency
#5
Vanessa A Evans, Renée M Van Der Sluis, Ajantha Solomon, Ashanti Dantanarayana, Catriona McNeil, Roger Garsia, Sarah Palmer, Rémi Fromentin, Nicolas Chomont, Rafick-Pierre Sékaly, Paul U Cameron, Sharon R Lewin
OBJECTIVE: In HIV-infected individuals on antiretroviral therapy (ART), latent HIV is enriched in CD4 T-cells expressing immune checkpoint molecules (ICs), in particular programmed cell death-1 (PD-1). We therefore assessed the effect of blocking PD-1 on latency, both in vitro and in vivo. METHODS: HIV latency was established in vitro following co-culture of resting CD4 T-cells with myeloid dendritic cells. Expression of PD-1 was quantified by flow cytometry, and latency assessed in sorted PD-1 and PD-1 non-proliferating CD4 memory T-cells...
May 9, 2018: AIDS
https://www.readbyqxmd.com/read/29743050/unmasking-of-intracranial-metastatic-melanoma-during-ipilimumab-nivolumab-therapy-case-report-and-literature-review
#6
Marin A McDonald, Parag Sanghvi, Julie Bykowski, Gregory A Daniels
BACKGROUND: While data from several studies over the last decade has demonstrated that introduction of immunologic checkpoint blockage therapy with anti-CTLA-4/PD-1 drugs leads to improved survival in metastatic melanoma patients, relatively little is known about brain-specific therapeutic response and adverse events in the context of immunotherapeutic treatment of intracranial disease. Here we report two independent cases of new intracranial metastases presenting after initiation of combined checkpoint blockade Ipilimumab and Nivolumab for recurrent metastatic melanoma in the context of positive systemic disease response...
May 9, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29721366/tnfa-and-il-2-armed-adenoviruses-enable-complete-responses-by-anti-pd-1-checkpoint-blockade
#7
V Cervera-Carrascon, M Siurala, J M Santos, R Havunen, S Tähtinen, P Karell, S Sorsa, A Kanerva, A Hemminki
Releasing the patient's immune system against their own malignancy by the use of checkpoint inhibitors is delivering promising results. However, only a subset of patients currently benefit from them. One major limitation of these therapies relates to the inability of T cells to detect or penetrate into the tumor resulting in unresponsiveness to checkpoint inhibition. Virotherapy is an attractive tool for enabling checkpoint inhibitors as viruses are naturally recognized by innate defense elements which draws the attention of the immune system...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29704887/the-sirna-mediated-downregulation-of-pd-1-alone-or-simultaneously-with-ctla-4-shows-enhanced-in-vitro-car-t-cell-functionality-for-further-clinical-development-towards-the-potential-use-in-immunotherapy-of-melanoma
#8
Bianca Simon, Dennis C Harrer, Beatrice Schuler-Thurner, Niels Schaft, Gerold Schuler, Jan Dörrie, Ugur Uslu
Chimeric antigen receptor (CAR)-T cells have been used successfully for cancer immunotherapy. While substantial tumor regression was observed in leukemia and lymphoma, CAR-therapy of solid tumors needs further improvement. A major obstacle to the efficiency of engineered T cells is posed by triggering of inhibitory receptors, e.g. programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), leading to an impaired anti-tumor activity. To boost CAR-T-cell function, we co-electroporated T cells with both, mRNA encoding a CAR specific for chondroitin sulfate proteoglycan 4 (CSPG4) and small-interfering RNAs (siRNAs) to downregulate PD-1 (siPD-1) and CTLA-4 (siCTLA-4)...
April 28, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29703161/survival-and-clinical-outcomes-of-patients-with-melanoma-brain-metastasis-in-the-era-of-checkpoint-inhibitors-and-targeted-therapies
#9
Elham Vosoughi, Jee Min Lee, James R Miller, Mehdi Nosrati, David R Minor, Roy Abendroth, John W Lee, Brian T Andrews, Lewis Z Leng, Max Wu, Stanley P Leong, Mohammed Kashani-Sabet, Kevin B Kim
BACKGROUND: Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. METHODS: We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015...
April 27, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29694419/t-cell-mediated-immunity-after-combination-therapy-with-intralesional-pv-10-and-blockade-of-the-pd-1-pd-l1-pathway-in-a-murine-melanoma-model
#10
Hao Liu, Amy Weber, Jennifer Morse, Krithika Kodumudi, Ellen Scott, John Mullinax, Amod A Sarnaik, Shari Pilon-Thomas
Intralesional (IL) injection of Rose Bengal (PV-10) induces regression of injected and uninjected lesions in several murine tumor models. In this study, we investigated the anti-tumor response of combining IL PV-10 with blockade of the PD-1 / PD-L1 pathway and the role of immune cell populations in eliciting this response. To investigate the role of T cell subsets in mediating an immune response, B16 or M05 melanoma-bearing mice received combination therapy as well as CD8+, CD4+, or CD25+ depleting antibodies...
2018: PloS One
https://www.readbyqxmd.com/read/29688262/t-cells-isolated-from-patients-with-checkpoint-inhibitor-resistant-melanoma-are-functional-and-can-mediate-tumor-regression
#11
R Andersen, T H Borch, A Draghi, A Gokuldass, M A H Rana, M Pedersen, M Nielsen, P Kongsted, J W Kjeldsen, M C W Westergaard, H D Radic, C A Chamberlain, L R Hölmich, H W Hendel, M S Larsen, Ö Met, I M Svane, M Donia
Background: The majority of patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses. Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-PD-1 and anti-CTLA-4 treatment...
April 24, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29677240/uveal-effusion-after-immune-checkpoint-inhibitor-therapy
#12
Merina Thomas, Stephen T Armenti, M Bernadete Ayres, Hakan Demirci
Importance: Immune checkpoint inhibitors, including antiprogrammed cell death protein-1 (anti-PD-1) and antiprogrammed cell death ligand-1 (anti-PD-L1) monoclonal antibodies, have recently been introduced as a promising new immunotherapy for solid cancers. The adverse effects typically include inflammation of the skin, endocrine, and gastrointestinal systems. Objective: To describe 3 patients who developed uveal effusion after initiating anti-PD-1 and anti-PD-L1 monoclonal antibody therapy...
April 12, 2018: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29673240/the-major-role-of-nf-kb-in-the-depth-of-invasion-on-acral-melanoma-by-decreasing-cd8-t-cells
#13
Hermin Aminah Usman, Bethy S Hernowo, Maringan Diapari Lumban Tobing, Reti Hindritiani
Background: The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor кB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response...
April 20, 2018: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/29669928/cx3cr1-identifies-pd-1-therapy-responsive-cd8-t-cells-that-withstand-chemotherapy-during-cancer-chemoimmunotherapy
#14
Yiyi Yan, Siyu Cao, Xin Liu, Susan M Harrington, Wendy E Bindeman, Alex A Adjei, Jin Sung Jang, Jin Jen, Ying Li, Pritha Chanana, Aaron S Mansfield, Sean S Park, Svetomir N Markovic, Roxana S Dronca, Haidong Dong
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti-PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of chemotherapy and are increased in patients with metastatic melanoma who responded to chemoimmunotherapy (paclitaxel and carboplatin plus PD-1 blockade)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29666298/delayed-autoimmune-toxicity-occurring-several-months-after-cessation-of-anti-pd-1-therapy
#15
Sagun Parakh, Jonathan Cebon, Oliver Klein
Treatment with anti-programmed cell death protein 1 (PD-1) antibodies has demonstrated clinical efficacy in a whole range of malignancies including advanced melanoma, renal cell cancer, bladder cancer, and non-small cell lung cancer. Immune-related adverse events are a unique side effect of checkpoint regulator therapy including anti-PD-1 antibodies. Treatment-related autoimmunity can occur in any organ system, with the median onset usually within 5-15 weeks from the commencement of therapy, depending on the organ system involved...
April 17, 2018: Oncologist
https://www.readbyqxmd.com/read/29665734/in-vivo-antitumor-effects-of-mk615-led-by-pd-l1-downregulation
#16
Masashi Yanaki, Masayuki Kobayashi, Atsushi Aruga, Minoru Nomura, Makoto Ozaki
BACKGROUND/AIM: MK615 extracted from Prunus mume was reported to have anti-inflammatory effects. In this article, we examined the in vivo antitumor effect of MK615 (an extract from Japanese apricot) using mouse tumor xenografts and focusing on the downregulation of PD-L1 (programmed death-ligand 1), a ligand of programmed cell death-1, a surface protein of activated T cells. MATERIALS AND METHODS: B16/BL6 melanoma cells were injected into C57BL/6 or BALB/c-nu/nu mice to establish lung metastasis...
April 1, 2018: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/29656892/cancer-germline-antigen-expression-discriminates-clinical-outcome-to-ctla-4-blockade
#17
Sachet A Shukla, Pavan Bachireddy, Bastian Schilling, Christina Galonska, Qian Zhan, Clyde Bango, Rupert Langer, Patrick C Lee, Daniel Gusenleitner, Derin B Keskin, Mehrtash Babadi, Arman Mohammad, Andreas Gnirke, Kendell Clement, Zachary J Cartun, Eliezer M Van Allen, Diana Miao, Ying Huang, Alexandra Snyder, Taha Merghoub, Jedd D Wolchok, Levi A Garraway, Alexander Meissner, Jeffrey S Weber, Nir Hacohen, Donna Neuberg, Patrick R Potts, George F Murphy, Christine G Lian, Dirk Schadendorf, F Stephen Hodi, Catherine J Wu
CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro...
April 6, 2018: Cell
https://www.readbyqxmd.com/read/29644214/anti-pd-1-and-anti-ctla-4-therapies-in-cancer-mechanisms-of-action-efficacy-and-limitations
#18
REVIEW
Judith A Seidel, Atsushi Otsuka, Kenji Kabashima
Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunotherapies, neutralizing antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as particularly successful. These antibodies have resulted in dramatic improvements in disease outcome and are now clinically approved in many countries...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29643991/serum-levels-of-soluble-cd163-and-cxcl5-may-be-predictive-markers-for-immune-related-adverse-events-in-patients-with-advanced-melanoma-treated-with-nivolumab-a-pilot-study
#19
Taku Fujimura, Yota Sato, Kayo Tanita, Yumi Kambayashi, Atsushi Otsuka, Yasuhiro Fujisawa, Koji Yoshino, Shigeto Matsushita, Takeru Funakoshi, Hiroo Hata, Yuki Yamamoto, Hiroshi Uchi, Yumi Nonomura, Ryota Tanaka, Megumi Aoki, Keisuke Imafuku, Hisako Okuhira, Sadanori Furudate, Takanori Hidaka, Setsuya Aiba
Antibodies against PD-1, such as nivolumab and pembrolizumab, are widely used in the treatment of various cancers including advanced melanoma. The anti-PD-1 Ab significantly prolongs survival in patients with metastatic melanoma, and its administration in combination with local or systemic therapy may also lead to improved outcomes. Although anti-PD-1 Ab-based combined therapy might be effective for the treatment of advanced melanoma, the associated risk of irAEs is an important consideration. Therefore, being able to predict irAEs is of great interest to oncologists...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29628796/immunotherapy-of-melanoma
#20
Iwona Lugowska, Pawel Teterycz, Piotr Rutkowski
The immunotherapy is currently changing the landscape of oncology. Nowadays the standard of care in metastatic or unresectable melanoma patients include immunomodulating modalities such as anti-PD-1 drugs (nivolumab, pembrolizumab) and anti-CTLA-4 antibody ipilimumab. The improvements of progression free survival and overall survival connected with those treatments were unprecedented and have been confirmed in stage III trials. The efficacy of immunotherapy in metastatic setting can be further upgraded in some groups of patients by combining both types of antibodies...
March 2018: Contemporary Oncology Współczesna Onkologia
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