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Melanoma pd-1

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https://www.readbyqxmd.com/read/29052782/clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#1
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29050517/the-safety-and-efficacy-of-dabrafenib-and-trametinib-for-the-treatment-of-melanoma
#2
Sarah Knispel, Lisa Zimmer, Theodora Kanaki, Selma Ugurel, Dirk Schadendorf, Elisabeth Livingstone
The introduction of BRAF and MEK inhibitors into clinical practice improved the prognosis of metastatic melanoma patients. The combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib has shown its superiority to single agent therapy and is characterized by a tolerable spectrum of adverse events which shows a decrease in incidence over time on treatment. Areas covered: The current scientific literature on safety and adverse events (AEs) related to BRAF and MEK-inhibition has been investigated with special focus on the large phase 3 studies (COMBI-v, COMBI-d and CoBRIM) as well as recent updates presented at oncology and melanoma meetings...
October 20, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29050354/phase-i-study-of-nivolumab-combined-with-ifn-%C3%AE-for-patients-with-advanced-melanoma
#3
Taku Fujimura, Takanori Hidaka, Yumi Kambayashi, Sadanori Furudate, Aya Kakizaki, Hisayuki Tono, Akira Tsukada, Takahiro Haga, Akira Hashimoto, Ryo Morimoto, Takuhiro Yamaguchi, Tadao Takano, Setsuya Aiba
The efficacy of nivolumab is greater than that of other anti-melanoma drugs, so nivolumab-based combined therapies that enhance anti-tumor immune responses in patients with metastatic melanoma are of great interest to dermato-oncologists. As we have previously reported, IFN-β enhances the anti-tumor immune response of anti-PD-1 antibodies against B16F10 melanoma in vivo. To explore the potential of this property of IFN-β as part of a combination therapy for the treatment of metastatic melanoma patients, we performed a phase 1 trial, using a traditional rule-based 3 + 3 design, on patients with advanced melanoma...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#4
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29045547/safety-of-resuming-anti-pd-1-in-patients-with-immune-related-adverse-events-iraes-during-combined-anti-ctla-4-and-anti-pd1-in-metastatic-melanoma
#5
M H Pollack, A Betof, H Dearden, K Rapazzo, I Valentine, A S Brohl, K K Ancell, G V Long, A M Menzies, Z Eroglu, D B Johnson, A N Shoushtari
Background: Combined CTLA-4 and PD-1 blockade induces high rates of immune-related adverse events (irAEs). The safety of resuming anti-PD-1 in patients who discontinue combination therapy due to irAEs is not known. Patients and Methods: We assessed patients who experienced clinically significant irAEs from combined CTLA-4 and PD-1 blockade leading to treatment discontinuation at four academic centers. We assessed the safety of resuming anti-PD-1 in terms of recurrent and distinct irAEs...
October 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29037215/melanoma-brain-metastases-treated-with-stereotactic-radiosurgery-and-concurrent-pembrolizumab-display-marked-regression-efficacy-and-safety-of-combined-treatment
#6
Erik S Anderson, Michael A Postow, Jedd D Wolchok, Robert J Young, Åse Ballangrud, Timothy A Chan, Yoshiya Yamada, Kathryn Beal
BACKGROUND: Brain metastases are common in patients with metastatic melanoma. With increasing numbers of melanoma patients on anti-PD-1 therapy, we sought to evaluate the safety and initial response of brain metastases treated with concurrent pembrolizumab and radiation therapy. METHODS: From an institutional database, we retrospectively identified patients with melanoma brain metastases treated with radiation therapy (RT) who received concurrent pembrolizumab. Concurrent treatment was defined as RT during pembrolizumab administration period and up to 4 months after most recent pembrolizumab treatment...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29036261/development-of-halo-nevi-in-a-lung-cancer-patient-a-novel-immune-related-cutaneous-event-from-atezolizumab
#7
Mathew R Birnbaum, Michelle W Ma, Michael A Casey, Bijal D Amin, Mark Jacobson, Haiying Cheng, Beth N McLellan
Immunotherapy-induced vitiligo is an immune-related adverse event (irAE) observed in metastatic melanoma patients treated with immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) pathways. To date, the development of leukoderma, poliosis, and halo nevi during immunotherapy has largely been reported in metastatic melanoma patients. We report a case of immunotherapy-induced leukoderma presenting as halo nevi in a patient with non-small cell lung cancer (NSCLC) treated with atezolizumab, a programmed cell death ligand (PD-L1) antibody...
October 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29034210/biomarkers-for-response-of-melanoma-patients-to-immune-checkpoint-inhibitors-a-systematic-review
#8
Charissa A C Jessurun, Julien A M Vos, Jacqueline Limpens, Rosalie M Luiten
BACKGROUND: Immune checkpoint inhibitors (ICIs), targeting CTLA-4 or PD-1 molecules, have shown impressive therapeutic results. However, only 20-40% of advanced melanoma patients have durable responses to ICI, and these positive effects must be balanced against severe off-target immune toxicity and high costs. This urges the development of predictive biomarkers for ICI response to select patients with likely clinical benefit from treatment. Although many candidate biomarkers exist, a systematic overview of biomarkers and their usefulness is lacking...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29033546/safety-and-efficacy-profile-of-pembrolizumab-in-solid-cancer-pooled-reanalysis-based-on-randomized-controlled-trials
#9
Manni Wang, Xuelei Ma, Linghong Guo, Fan Xia
BACKGROUND: The aim of the present review is to systematically evaluate the efficacy and safety of pembrolizumab by analyzing survival outcomes and at the same time, to present evidence for future clinical applications of anti-programmed cell death protein 1 (anti-PD-1) antibodies by analyzing the efficacy and safety of pembrolizumab. METHODS: A comprehensive literature search of PubMed, Medline, and Embase was performed for all relevant clinical trials. In this study, adverse events of any grades and grades ≥3 were summarized and calculated for event rates...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29029813/innovative-therapy-monoclonal-antibodies-and-beyond
#10
M Di Nicola, L Apetoh, M Bellone, M P Colombo, G Dotti, S Ferrone, M Muscolini, J Hiscott, A Anichini, S M Pupa, F de Braud, M Del Vecchio
The seventh Edition of "Innovative Therapy, Monoclonal Antibodies and Beyond" Meeting took place in Milan, Italy, on January 27, 2017. The two sessions of the meeting were focused on: 1) Preclinical assays and novel biotargets; and 2) monoclonal antibodies, cell therapies and targeted molecules. Between these two sessions, a lecture entitled "HLA-antigens modulation and response to immune checkpoint inhibitor immunotherapy" was also presented. Despite the impressive successes in cancer immunotherapy in recent years, the response to immune based interventions occurs only in a minority of patients (∼20%)...
October 5, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29028789/safe-administration-of-an-anti-pd-1-antibody-to-kidney-transplant-patients-2-clinical-cases-and-review-of-the-literature
#11
Julia K Winkler, Ralf Gutzmer, Carolin Bender, Nina Lang, Martin Zeier, Alexander H Enk, Jessica C Hassel
Antiprogrammed cell-death protein 1 (PD-1) antibodies have revolutionized therapy of metastatic melanoma and other tumors, but some subgroups of patients such as immunosuppressed patients after solid-organ transplantation, have regularly been excluded from clinical studies. We report 2 cases of kidney-transplant patients who received an anti-PD-1 antibody to treat metastatic melanoma. Treatment was tolerated well with no relevant adverse events and stable kidney functions, but the melanoma progressed in both patients...
November 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29028121/lupus-like-cutaneous-reaction-following-pembrolizumab-an-immune-related-adverse-event-associated-with-anti-pd-1-therapy
#12
Kimberly Shao, Suzanne McGettigan, Rosalie Elenitsas, Emily Y Chu
PD-1 (programmed cell death-1) inhibitors, used to treat metastatic melanoma and other malignancies, are associated with development of immune-related adverse events in the skin. Such reactions include morbilliform eruptions, vitiligo, alopecia areata, and bullous pemphigoid. In this report, we describe a patient who developed a lupus-like cutaneous reaction in the setting of pembrolizumab therapy for metastatic melanoma, adding to the spectrum of reactions which may be observed in association with PD-1 inhibitor therapy...
October 13, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29026335/challenging-the-standard-of-care-in-advanced-melanoma-focus-on-pembrolizumab
#13
REVIEW
Raghad M Abdul-Karim, C Lance Cowey
The last several years have seen a dramatic rise in the number of effective therapies that have been shown to improve survival outcomes for patients with advanced melanoma. Among these treatments are the immune checkpoint inhibitors, a new class of immunotherapy, that have demonstrated the ability to improve both response rates and survival outcomes. Pembrolizumab, an immune checkpoint inhibitor that blocks the negative regulatory PD-1 receptor on T-cell lymphocytes, has shown improved efficacy compared to standard therapies with an acceptable tolerability profile...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/29024572/radiological-manifestations-of-immune-related-adverse-effects-observed-in-patients-with-melanoma-undergoing-immunotherapy
#14
Parveen Sidhu, Alexander M Menzies, Georgina Long, Matteo Carlino, Shirleen Lorens, Rony Kapoor
Immunotherapy drugs work by stimulating the patient's own immune system to recognize and destroy cancer cells. This subclass of drugs is increasingly administered to patients with advanced melanoma. They are also commonly incorporated into other cancer therapies such as non-small cell lung cancer, renal cancer, head and neck cancers and Hodgkin lymphoma. The most commonly administered immunotherapeutic agents in the treatment of melanoma include programmed cell death protein 1 (PD-1) inhibitors, cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors and a subclass of cytokines...
October 11, 2017: Journal of Medical Imaging and Radiation Oncology
https://www.readbyqxmd.com/read/29024038/baseline-lab-parameters-predicting-clinical-outcome-in-melanoma-patients-treated-with-ipilimumab-a-single-center-analysis
#15
Thilo Gambichler, Victoria Brown, Ann-Kathrin Steuke, Lutz Schmitz, Eggert Stockfleth, Laura Susok
BACKGROUND: Overall response rates (ORR) for ipilimumab in advanced melanoma are only about 10%. Hence, it is important to explore biomarkers predicting ipilimumab responders. OBJECTIVE: We aimed to explore biomarkers in order to predict therapy outcome in melanoma patients who have undergone standard ipilimumab therapy in a real-world setting. METHODS: Databases of cutaneous melanoma patients (n = 52) who had received ipilimumab were reviewed and data collected on patient characteristics and diverse lab parameters...
October 10, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29020960/perspectives-in-immunotherapy-meeting-report-from-the-immunotherapy-bridge-napoli-november-30th-2016
#16
Paolo A Ascierto, Bruno Daniele, Hans Hammers, Vera Hirsh, Joseph Kim, Lisa Licitra, Rita Nanda, Sandro Pignata
The complex interactions between the immune system and tumors lead the identification of key molecules that govern these interactions: immunotherapeutics were designed to overcome the mechanisms broken by tumors to evade immune destruction. After the substantial advances in melanoma, immunotherapy currently includes many other type of cancers, but the melanoma lesson is essential to progress in other type of cancers, since immunotherapy is potentially improving clinical outcome in various solid and haematologic malignancies...
October 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29018908/characterization-of-arthralgia-induced-by-pd-1-antibody-treatment-in-patients-with-metastasized-cutaneous-malignancies
#17
Kristina Buder-Bakhaya, Karolina Benesova, Carsten Schulz, Hoda Anwar, Antonia Dimitrakopoulou-Strauss, Tim F Weber, Alexander Enk, Hanns-Martin Lorenz, Jessica C Hassel
BACKGROUND: PD-1 antibodies (PD1ab) are increasingly used in metastatic melanoma and other malignancies. Arthralgia is an underestimated side effect of PD-1 antibody treatment with unknown cause. Our aim was to characterize PD1ab-induced arthralgia. PATIENTS AND METHODS: We retrospectively included patients with metastatic cutaneous malignancies treated with pembrolizumab or nivolumab ± ipilimumab at the National Center for Tumor Diseases (Heidelberg) between 01/2013 and 09/2016...
October 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28988442/dramatic-response-to-nivolumab-in-xeroderma-pigmentosum-skin-tumor
#18
Fanny Chambon, Sophie Osdoit, Kelly Bagny, Anne Moro, Jacqueline Nguyen, Yves Réguerre
We report the case of a 6-year-old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti-programmed cell death protein 1 (anti-PD-1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected...
October 8, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28985469/programmed-cell-death-protein-ligand-1-silencing-with-polyethylenimine-dermatan-sulfate-complex-for-dual-inhibition-of-melanoma-growth
#19
Gijung Kwak, Dongkyu Kim, Gi-Hoon Nam, Sun Young Wang, In-San Kim, Sun Hwa Kim, Ick-Chan Kwon, Yoon Yeo
Programmed cell death protein-1 (PD-1) is a prominent immune checkpoint receptor interacting with its ligand, programmed cell death protein ligand-1 (PD-L1, B7-H1). The PD-1/PD-L1 interaction induces functional exhaustion of tumor-reactive cytotoxic T cells and, thus, interferes with antitumor T-cell immunity. In addition, PD-1/PD-L1 interaction promotes tumorigenesis via the mTOR signaling pathway in a group of cancers including melanoma. Based on the dual functions of PD-1/PD-L1 interactions in tumor progression, we hypothesize that siRNA targeting PD-L1 (siPD-L1) will suppress melanoma growth, acting on both immune checkpoint and intrinsic tumorigenesis pathways...
October 12, 2017: ACS Nano
https://www.readbyqxmd.com/read/28984690/pd-1-pd-l1-and-vegf-a-vegf-c-expression-in-lymph-node-microenvironment-and-association-with-melanoma-metastasis-and-survival
#20
Cristina Alessi, Cristovam Scapulatempo Neto, Cristiano R Viana, Vinicius de Lima Vazquez
Regional lymph nodes are affected frequently by melanoma metastasis. Its microenvironment may be associated with tumor progression. We investigated sentinel nodes with and without tumor and negative nodes surrounding positive nodes, looking for patterns related to tumor immune interaction and lymphovascular progression. We quantified programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1, vascular endothelial growth factor (VEGF)-A/VEGF-C expressions in lymph nodes of 103 patients who underwent sentinel lymph node biopsy...
October 3, 2017: Melanoma Research
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