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https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#1
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28327969/circulating-tumour-dna-predicts-response-to-anti-pd1-antibodies-in-metastatic-melanoma
#2
J H Lee, G V Long, S Boyd, S Lo, A M Menzies, V Tembe, A Guminski, V Jakrot, R A Scolyer, G J Mann, R F Kefford, M S Carlino, H Rizos
Background: Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information. Patients and methods: We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab. Results: ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#3
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28323504/pembrolizumab-use-for-the-treatment-of-advanced-melanoma
#4
Pol Specenier
Until recently, overall long term survival in patients with stage IV melanoma was lower than 10 %. However, the treatment of melanoma has evolved rapidly over the last few years, with the advent of inhibitors of BRAF and MEK and of immunotherapeutic agents including ipilimumab, nivolumab, and pembrolizumab. Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma...
March 21, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28321815/immune-therapy-for-sarcomas
#5
Peter M Anderson
Absolute lymphocyte count (ALC) recovery rapidly occurring at 14 days after start of chemotherapy for osteosarcoma and Ewing sarcoma is a good prognostic factor. Conversely, lymphopenia is associated with significantly decreased sarcoma survival. Clearly, the immune system can contribute towards better survival from sarcoma. This chapter will describe treatment and host factors that influence immune function and how effective local control and systemic interventions of sarcoma therapy can cause inflammation and/or immune suppression but are currently the standard of care...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321813/harnessing-the-immune-system-against-leukemia-monoclonal-antibodies-and-checkpoint-strategies-for-aml
#6
Lucia Masarova, Hagop Kantarjian, Guillermo Garcia-Mannero, Farhad Ravandi, Padmanee Sharma, Naval Daver
Acute myeloid leukemia (AML) is the most common leukemia among adults and is associated with a poor prognosis, especially in patients with adverse prognostic factors, older age, or relapsed disease. The last decade has seen a surge in successful immune-based therapies in various solid tumors; however, the role of immune therapies in AML remains poorly defined. This chapter describes the rationale, clinical data, and toxicity profiles of immune-based therapeutic modalities in AML including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD1/PDL1 or CTLA4...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#7
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28318492/-brain-tumor-immunotherapy-illusion-or-hope
#8
REVIEW
Denis Migliorini, Valérie Dutoit, Paul R Walker, Pierre-Yves Dietrich
Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials...
March 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28314785/tumor-localized-secretion-of-soluble-pd1-enhances-oncolytic-virotherapy
#9
Mee Y Bartee, Katherine M Dunlap, Eric Bartee
Oncolytic virotherapy represents an attractive option for the treatment of a variety of aggressive or refractory tumors. While this therapy is effective at rapidly debulking directly injected tumor masses, achieving complete eradication of established disease has proven difficult. One method to overcome this challenge is to use oncolytic viruses to induce secondary anti-tumor immune responses. Unfortunately, while the initial induction of these immune responses is typically robust, their subsequent efficacy is often inhibited through a variety of immunoregulatory mechanisms, including the PD1/PDL1 T-cell checkpoint pathway...
March 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28279082/effects-of-immunization-and-checkpoint-inhibition-on-amodiaquine-induced-liver-injury
#10
Alastair Mak, Alexander Johnston, Jack Uetrecht
If idiosyncratic drug-induced liver injury (IDILI) is immune-mediated, it is possible that an individual's prior exposure to antigens may affect their susceptibility to IDILI. An individual's repertoire of memory immune cells is shaped by every past exposure to antigens. Subsequent drug-induced adverse drug reactions may therefore involve an immune cell's cross reactivity between a prior antigen and resulting drug-modified proteins. Therefore in this experiment, mice were immunized with amodiaquine (AQ)-modified hepatic proteins to mimic a previous exposure; treated with a RIBI adjuvant and anti-CD40 antibodies to stimulate an immune response; and, treated with anti-PD1 and anti-CTLA-4 antibodies prior to AQ treatment in order to overcome immune tolerance...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28264791/more-than-5000-patients-with-metastatic-melanoma-in-europe-per-year-do-not-have-access-to-recommended-first-line-innovative-treatments
#11
L Kandolf Sekulovic, K Peris, A Hauschild, A Stratigos, J-J Grob, P Nathan, R Dummer, A-M Forsea, C Hoeller, H Gogas, L Demidov, C Lebbe, C Blank, J Olah, L Bastholt, D Herceg, B Neyns, R Vieira, J Hansson, P Rutkowski, I Krajsova, M Bylaite-Bucinskiene, I Zalaudek, J Maric-Brozic, N Babovic, M Banjin, K Putnik, G Weinlich, V Todorovic, K Kirov, J Ocvirk, A Zhukavets, M Kukushkina, L De La Cruz Merino, A Ymeri, M Risteski, C Garbe
BACKGROUND: Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF)...
March 2, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28236768/survival-of-patients-with-melanoma-brain-metastasis-treated-with-stereotactic-radiosurgery-and-active-systemic-drug-therapies
#12
Ee Siang Choong, Serigne Lo, Martin Drummond, Gerald B Fogarty, Alexander M Menzies, Alexander Guminski, Brindha Shivalingam, Kathryn Clarke, Georgina V Long, Angela M Hong
INTRODUCTION: With new systemic therapies demonstrating activity in melanoma brain metastasis, most of the previously reported stereotactic radiosurgery (SRS) data are superseded. In this study, we report the outcomes (overall survival [OS] and brain control [BC]) and identify factors that associate with such outcomes in the era of modern systemic therapy. METHOD: A total of 108 patients treated with SRS from 2010 to 2015 were included. Systemic treatment use within 6 weeks of SRS was noted...
February 22, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28197389/adaptive-resistance-to-anti-pd1-therapy-by-tim-3-upregulation-is-mediated-by-the-pi3k-akt-pathway-in-head-and-neck-cancer
#13
Gulidanna Shayan, Raghvendra Srivastava, Jing Li, Nicole Schmitt, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28188133/pd1-blockade-with-pembrolizumab-is-highly-effective-in-relapsed-or-refractory-nk-t-cell-lymphoma-failing-l-asparaginase
#14
Yok-Lam Kwong, Thomas S Y Chan, Daryl Tan, Seok Jin Kim, Li-Mei Poon, Benjamin Mow, Pek-Lan Khong, Florence Loong, Rex Au-Yeung, Jabed Iqbal, Colin Phipps, Eric Tse
Natural killer (NK)/T-cell lymphomas failing L-asparaginse-regimens have no known salvage and are almost invariably fatal. Seven male NK/T-cell lymphoma patients (age: 49, 31-68, years) failing 2 (1-5) regimens (including L-asparaginase-regimens, and allogeneic hematopoietic stem cell transplantation, HSCT, in 2 cases), were treated with the anti-programmed-death-1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic and molecular (circulating Epstein-Barr virus, EBV, DNA) criteria...
February 10, 2017: Blood
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#15
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28180238/atrophic-exocrine-pancreatic-insufficiency-associated-with-anti-pd1-therapy
#16
A Hoadley, N Sandanayake, G V Long
No abstract text is available yet for this article.
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28179176/peri-srs-administration-of-immune-checkpoint-therapy-for-melanoma-metastatic-to-the-brain-investigating-efficacy-and-the-effects-of-relative-treatment-timing-on-lesion-response
#17
Mehran B Yusuf, Mark J Amsbaugh, Eric Burton, Jason Chesney, Shiao Woo
OBJECTIVE(S): To investigate the efficacy of immune checkpoint therapy (ICT) administered with stereotactic radiosurgery (SRS) and determine the effects of relative treatment timing on lesion response. METHODS: A prospective institutional database of all patients with intact brain metastases treated with SRS from 2007 to 2015 was reviewed for patients diagnosed with malignant melanoma. Lesion response was determined using a modified RECIST v1.1 criteria. Patients were grouped according to if they received ICT and the timing of ICT relative to SRS...
February 4, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28159404/-pd1-pd-l1-immunohistochemistry-in-thoracic-oncology-where-are-we
#18
Paul Hofman, Marius Ilié, Sandra Lassalle, Elodie Long, Coraline Bence, Catherine Butori, Véronique Hofman
The assays for the assessment of the PD-L1 status by immunohistochemistry are available in clinical studies in thoracic oncology to predict response to immunotherapies targeting the PD-1/PD-L1 pathway. With the arrival of this new class of molecules in second line and very soon in first line of treatment for patients with advanced or metastatic non-small cell lung cancer, these tests will certainly be required in routine once these new drugs will be granted marketing authorization. The rapid introduction of these "companion" or "complementary" tests seems essential to select patients to benefit from these effective but also expensive and sometimes toxic therapies...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28152786/first-line-treatment-of-metastatic-nsclc-mnsclc-patients-without-actionable-mutations-in-u-s-community-oncology-clinical-practice
#19
Ashwini Arunachalam, Thomas A Burke, Xiting Cao, Amy P Abernethy, David Paul Carbone
307 Background: Benchmarking high quality care requires defining optimally effective practice patterns. As first step, contemporary real-world practice must be detailed. The purpose of this study is to describe patient flow from diagnosis of mNSCLC to initiation of anti-cancer drug therapy in patients without known EGFR/ALK genomic tumor aberrations; the characteristics and first-line (1L) anti-cancer treatment of these patients, including induction and maintenance therapy. METHODS: Retrospective database cohort study using data from an oncology EHR system, representing 17% of incident cancer cases from US community setting...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28151378/checkpoint-inhibition-new-treatment-options-in-urologic-cancer
#20
Daan Joost De Maeseneer, Brant Delafontaine, Sylvie Rottey
Both urothelial (UC) and renal cell cancer (RCC) are highly immunogenic tumours. Recent advances in cellular immunity understanding have resulted in a successful new class of therapeutic agents. Interaction between the programmed cell death 1 (PD1) on regulatory T-cells (Treg) and programmed cell death 1 ligand (PDL1) on cancer cells inhibits an effective immune response and is an important mechanism for cancer cells to evade the immune system. Monoclonal anti-PD1 and anti-PDL1 antibodies inhibit this interaction and are called checkpoint inhibitors...
February 2017: Acta Clinica Belgica
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