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Anti-PD1

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https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#1
REVIEW
Zachary Benson, Saeed H Manjili, Mehran Habibi, Georgi Guruli, Amir A Toor, Kyle K Payne, Masoud H Manjili
Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy...
August 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28783540/survival-of-melanoma-patients-treated-with-targeted-therapy-and-immunotherapy-after-systematic-upfront-control-of-brain-metastases-by-radiosurgery
#2
C Gaudy-Marqueste, A S Dussouil, R Carron, L Troin, N Malissen, A Loundou, S Monestier, S Mallet, M A Richard, J M Régis, J J Grob
BACKGROUND: Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented. PATIENTS AND METHODS: Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice...
August 4, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28753231/pd-1-inhibitor-associated-lichenoid-inflammation-with-incidental-suprabasilar-acantholysis-or-vesiculation-report-of-four-cases
#3
Shaun Chou, Cathy Zhao, Shelley Ji Eun Hwang, Pablo Fernandez-Penas
BACKGROUND: Immune checkpoint agents targeting Programmed cell death-1 protein (PD1) or Cytotoxic T-Lymphocyte Associated Protein-4 (CTLA-4) receptors are increasingly utilised in treatment of advanced malignancies. However, these immunotherapies are commonly associated with idiosyncratic cutaneous adverse reactions. Thus, recognition and awareness of these reactions are necessary. METHODS: We reviewed the skin biopsies of all patients on anti-PD1 therapy with or without ipilimumab who developed lichenoid inflammation and included those with microscopic suprabasal or intraepidermal clefts...
July 28, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28739711/adrenal-insufficiency-related-to-anti-programmed-death-1-therapy
#4
Ryo Ariyasu, Atsushi Horiike, Takahiro Yoshizawa, Yosuke Dotsu, Junji Koyama, Masafumi Saiki, Tomoaki Sonoda, Shingo Nishikawa, Satoru Kitazono, Noriko Yanagitani, Makoto Nishio
BACKGROUND/AIM: Adrenal insufficiency is one of the adverse events (AEs) associated with anti-programmed death-1 (PD1) therapy. Delaying diagnoses can lead to serious conditions. It is necessary to elucidate detailed clinical features of these AEs. PATIENTS AND METHODS: Patients treated with anti-PD-1 monotherapy or in combination with anti-cytotoxic T cell lymphocyte-4 therapy at our hospital from January 2013 to December 2016 were identified. The patients' clinical characteristics and laboratory and radiologic findings were collected...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28735186/development-of-a-robust-reporter-gene-assay-to-measure-the-bioactivity-of-anti-pd-1-anti-pd-l1-therapeutic-antibodies
#5
Lan Wang, Chuanfei Yu, Yalan Yang, Kai Gao, Junzhi Wang
Being regarded as the 'cancer panacea', the anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs) have become the R&D focus of biopharmaceutical industries. Several marketed such mAbs have been proved particularly effective in treating various cancers. However, the cell-based bioassay to measure the biological activities of the anti-PD-1/anti-PD-L1 mAbs as the lot release or stability test has been a great challenge to quality control laboratories due to the immunomodulating nature of the mAbs. Here, we describe the development and validation of a reporter gene assay consisting of two-cell systems to measure the bioactivity of the anti-PD-1/anti-PD-L1 mAbs...
May 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#6
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733528/analyses-of-selected-safety-endpoints-in-phase-1-and-late-phase-clinical-trials-of-anti-pd-1-and-pd-l1-inhibitors-prediction-of-immune-related-toxicities
#7
Ricardo Costa, Rubens B Costa, Sarah M Talamantes, Irene Helenoswki, Benedito A Carneiro, Young Kwang Chae, William J Gradishar, Razelle Kurzrock, Francis J Giles
PURPOSE: Anti-PD1 and PD-L1 antibodies are associated with immune-related adverse effects (irAEs). This analysis aims to assess the discrepancies between frequencies of irAEs observed in phase 1 trials with those seen in late-phase trials and to evolve the field of drug development. METHODS: PubMed search was conducted for articles published until December of 2016. Trials needed to have at least one of the study arms consisting of nivolumab, pembrolizumab or atezolizumab monotherapy...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28725344/complete-response-of-mediastinal-clear-cell-sarcoma-to-pembrolizumab-with-radiotherapy
#8
Samuel Marcrom, Jennifer F De Los Santos, Robert M Conry
BACKGROUND: Clear cell sarcoma (CCS) is a rare, aggressive soft tissue sarcoma thought to derive from neural crest and characterized by a 12;22 translocation. The resulting fusion protein directly activates expression of the melanocyte master transcription factor and drives the same down-stream pathways in CCS and melanoma leading to significant clinical parallels between these malignancies. Striking success of immune checkpoint blockade in melanoma has promoted interest in immunotherapy of CCS...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28707403/melanocytic-lesion-evolution-patterns-with-targeted-therapies-and-immunotherapies-for-advanced-metastatic-melanoma-an-observational-study
#9
Cathy Yunjia Zhao, Shelley Ji Eun Hwang, Deepal Wakade, Giuliana Carlos, Rachael Anforth, Pablo Fernández-Peñas
BACKGROUND/OBJECTIVES: Various cutaneous side-effects have been reported with anti-melanoma systemic therapies. This study investigated the changes in melanocytic lesion pigmentation in patients on four different therapies. METHODS: We analysed the serial dermatoscopic photographs of atypical melanocytic lesions taken from patients with advanced metastatic melanoma on four different systemic therapies (selective BRAF-inhibitor monotherapy, dabrafenib combined with trametinib [D&T], anti-programmed cell death protein 1 [anti-PD1] therapies, and anti-PD1 combined with ipilimumab) seen from February 2013 to May 2016...
July 14, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28707167/supportive-care-for-patients-undergoing-immunotherapy
#10
Bernardo Leon Rapoport, Ronwyn van Eeden, Vincent Sibaud, Joel B Epstein, Jean Klastersky, Matti Aapro, Devan Moodley
Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections...
July 13, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28700789/hair-repigmentation-during-immunotherapy-treatment-with-an-anti-programmed-cell-death-1-and-anti-programmed-cell-death-ligand-1-agent-for-lung-cancer
#11
Noelia Rivera, Aram Boada, M Isabel Bielsa, M Teresa Fernández-Figueras, Enric Carcereny, M Teresa Moran, Carlos Ferrándiz
Importance: New targeted therapies for cancer have been released in recent years, opening new horizons in the treatment of patients with cancer. However, their related adverse events (AE) are not fully characterized. Hair repigmentation (HR) is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of lung cancer (LC), in opposition to the vitiligo reactions that develop during melanoma treatment...
July 12, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28662677/a-phase-i-ii-trial-of-fixed-dose-stereotactic-body-radiotherapy-with-sequential-or-concurrent-pembrolizumab-in-metastatic-urothelial-carcinoma-evaluation-of-safety-and-clinical-and-immunologic-response
#12
Nora Sundahl, Katrien De Wolf, Sylvie Rottey, Karel Decaestecker, Daan De Maeseneer, Annabel Meireson, Els Goetghebeur, Valérie Fonteyne, Sofie Verbeke, Pieter De Visschere, Dries Reynders, Mireille Van Gele, Lieve Brochez, Piet Ost
BACKGROUND: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment...
June 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28661584/clinical-and-palliative-care-outcomes-for-patients-of-poor-performance-status-treated-with-antiprogrammed-death-1-monoclonal-antibodies-for-advanced-melanoma
#13
Annie Wong, Molly Williams, Donna Milne, Kortnye Morris, Peter Lau, Odette Spruyt, Sonia Fullerton, Grant McArthur
BACKGROUND: Antiprogrammed death-1 antibodies (anti-PD1) have response rates of 40% in metastatic melanoma. Patients with poor performance status (PS) were excluded from clinical trials, yet use of anti-PD1 is widespread in clinical practice. Literature regarding clinical and palliative care outcomes in patients with poor PS treated with anti-PD1 is lacking. METHODS: Retrospective review of outcomes for all patients with advanced melanoma treated with anti-PD1 between 2012 and June 2015 at Peter MacCallum Cancer Centre, a tertiary specialist cancer center in Australia...
June 29, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#14
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28636292/-head-and-neck-cancer-promising-results-of-immunotherapy
#15
Aurélie Sivade, Djamila Bensaid, Yan Monnier, Keyvan Shabafrouz, Hanan Bouchaab, Valérie Cristina
Immunotherapy, especially checkpoint inhibitors such as anti-PD1 and anti-PDL1 antibodies, has changed the standard of care and the prognosis of melanoma, but also more recently of lung cancer, renal cancer and Hodgkin lymphoma. Results of preliminary studies in head and neck squamous cell carcinoma (HNSCC) as well as in less frequent tumors of the region, such as nasopharyngeal carcinoma and high grade salivary gland carcinoma, are also promising. Indeed, in a recent phase 3 study, the PD1 inhibitor nivolumab has recently demonstrated a significant improvement in overall survival for platin-resistant recurrent and/or metastatic HNSCC...
May 17, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28616701/predictive-value-of-pd-l1-based-on-mrna-level-in-the-treatment-of-stage-iv-melanoma-with-ipilimumab
#16
C Brüggemann, M C Kirchberger, S M Goldinger, B Weide, A Konrad, M Erdmann, D Schadendorf, R S Croner, L Krähenbühl, K C Kähler, C Hafner, W Leisgang, F Kiesewetter, R Dummer, G Schuler, M Stürzl, L Heinzerling
INTRODUCTION: PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult...
June 14, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28613923/the-era-of-checkpoint-blockade-in-lung-cancer-taking-the-brakes-off-the-immune-system
#17
Edmund K Moon, Corey J Langer, Steven M Albelda
Despite recent advances with targeted kinase inhibitors and better-tolerated chemotherapy, the treatment of metastatic non-small-cell lung cancer remains suboptimal. One recent advance that holds great promise is immunotherapy-an approach that enhances a patient's immune system to better recognize and react to abnormal cells. The most successful immunotherapeutic strategy to date uses antibodies to block inhibitory receptors (also called "checkpoints") that are up-regulated on the T cells that infiltrate the tumor...
August 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28611624/flare-up-of-rheumatoid-arthritis-by-anti-ctla-4-antibody-but-not-by-anti-pd1-therapy-in-a-patient-with-metastatic-melanoma
#18
Nicoletta F Jaberg-Bentele, Michael Kunz, Shatha Abuhammad, Reinhard Dummer
A 47-year-old female patient with rheumatoid arthritis (RA) treated with methotrexate, was diagnosed with metastatic melanoma. After surgical removal of the tumor, the patient started treatment with ipilimumab while methotrexate was stopped. One week after initiation of ipilimumab, the patient developed typical symptoms of RA. Analgetic therapy was started. After 4 cycles of ipilimumab, melanoma progression was radiologically evident. The treatment plan was changed to pembrolizumab (anti-PD1 antibody), and the patient did not show active signs of RA anymore...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28601918/osimertinib-reactivated-immune-related-colitis-after-treatment-with-anti-pd1-antibody-for-non-small-cell-lung-cancer
#19
Tomoyoshi Takenaka, Koji Yamazaki, Naoko Miura, Naohiko Harada, Sadanori Takeo
We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea...
June 10, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28597150/erratum-to-sarcopenic-overweight-is-associated-with-early-acute-limiting-toxicity-of-anti-pd1-checkpoint-inhibitors-in-melanoma-patients
#20
Valentine Heidelberger, François Goldwasser, Nora Kramkimel, Anne Jouinot, Olivier Huillard, Pascaline Boudou-Rouquette, Johan Chanal, Jennifer Arrondeau, Nathalie Franck, Jérôme Alexandre, Benoît Blanchet, Karen Leroy, Marie-Françoise Avril, Nicolas Dupin, Sélim Aractingi
No abstract text is available yet for this article.
August 2017: Investigational New Drugs
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