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Immunotherapy ctla-4

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https://www.readbyqxmd.com/read/28224120/oncolytic-virotherapy-including-rigvir-and-standard-therapies-in-malignant-melanoma
#1
REVIEW
Hani M Babiker, Irbaz Bin Riaz, Muhammad Husnain, Mitesh J Borad
The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor), nivolumab (IgG4 PD-1 inhibitor), pembrolizumab (IgG4 PD-1 inhibitor) and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor) and trametinib (MEK inhibitor), as they yielded improved responses and survival in malignant melanoma patients...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#2
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28210995/checkpoint-inhibitors-for-the-treatment-of-renal-cell-carcinoma
#3
REVIEW
Pooja Ghatalia, Matthew Zibelman, Daniel M Geynisman, Elizabeth R Plimack
The advent of checkpoint inhibitors has revolutionized systemic therapy for many malignancies, including renal cell carcinoma (RCC) where multiple PD-1, PD-L1, and CTLA-4 inhibitors have demonstrated responses and improved survival for patients in clinical trials. Durable benefit with manageable toxicity can be achieved with these agents-but unfortunately for only a minority of individuals. Efforts are ongoing to understand mechanisms driving the response and resistance to checkpoint inhibitors in order to personalize therapy and extend benefit to more patients...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28202513/myeloid-cells-that-impair-immunotherapy-are-restored-in-melanomas-which-acquire-resistance-to-braf-inhibitors
#4
Shannon M Steinberg, Tamer Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian Malik, Tammara Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael Whitfield, Mary Jo Turk
Acquired resistance to BRAFV600E inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given the plastic nature of cancers. While there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment initially reduced by BRAFi treatment...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28199983/a-versatile-system-for-rapid-multiplex-genome-edited-car-t-cell-generation
#5
Jiangtao Ren, Xuhua Zhang, Xiaojun Liu, Chongyun Fang, Shuguang Jiang, Carl H June, Yangbing Zhao
The therapeutic potential of CRISPR system has already been demonstrated in many instances and begun to overlap with the rapidly expanding field of cancer immunotherapy, especially on the production of genetically modified T cell receptor or chimeric antigen receptor (CAR) T cells. Efficient genomic disruption of multiple gene loci to generate universal donor cells, as well as potent effector T cells resistant to multiple inhibitory pathways such as PD-1 and CTLA4 is an attractive strategy for cell therapy...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198830/-final-common-pathway-of-human-cancer-immunotherapy-targeting-random-somatic-mutations
#6
REVIEW
Eric Tran, Paul F Robbins, Steven A Rosenberg
Effective clinical cancer immunotherapies, such as administration of the cytokine IL-2, adoptive cell transfer (ACT) and the recent success of blockade of the checkpoint modulators CTLA-4 and PD-1, have been developed without clear identification of the immunogenic targets expressed by human cancers in vivo. Immunotherapy of patients with cancer through the use of ACT with autologous lymphocytes has provided an opportunity to directly investigate the antigen recognition of lymphocytes that mediate cancer regression in humans...
February 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28197360/enhancing-the-clinical-coverage-and-anticancer-efficacy-of-immune-checkpoint-blockade-through-manipulation-of-the-gut-microbiota
#7
Jonathan M Pitt, Marie Vétizou, Ivo Gomperts Boneca, Patricia Lepage, Mathias Chamaillard, Laurence Zitvogel
Although anticancer therapy with immune checkpoint blockers has seen unprecedented success, it fails to control neoplasia in most patients and often causes immune-related adverse events (irAEs). Our recent research shows the immunostimulatory and antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species of the gut microbiota, signifying novel approaches to improve such immunotherapies.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#8
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/28184224/cbl-b-deficiency-mediates-resistance-to-programmed-death-ligand-1-programmed-death-1-regulation
#9
Mai Fujiwara, Emily J Anstadt, Robert B Clark
Casitas B-lineage lymphoma-b (Cbl-b) is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) T cells are hyper-reactive and co-stimulation independent, and Cbl-b(-/-) mice demonstrate robust T cell and NK cell-mediated antitumor immunity. As a result of these murine studies, Cbl-b is considered a potential target for therapeutic manipulation in human cancer immunotherapy. The PD-L1/PD-1 pathway of immune regulation is presently an important therapeutic focus in tumor immunotherapy, and although Cbl-b(-/-) mice have been shown to be resistant to several immuno-regulatory mechanisms, the sensitivity of Cbl-b(-/-) mice to PD-L1-mediated suppression has not been reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28160999/-the-immune-checkpoints-how-does-it-work
#10
Clémence Granier, Vassili Soumelis, Marion Mandavit, Laure Gibault, Radia Belazzoug, Eléonore de Guillebon, Cécile Badoual, Eric Tartour, Hélène Roussel
Costimulatory molecules allow the full lymphocyte activation, whereas co-inhibitory molecules are negative counterparts that act as immune regulators, avoiding excessive response. In some context of chronic inflammation such as cancer, co-inhibitory immune checkpoint as CTLA-4, PD-1, Lag-3, Tim-3 can accumulate at the membrane of T cells leading to a state of anergy and therefore the loss of tumor growth control. Consequently, these immune checkpoints are considered as potential target in the treatment of cancer...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28129117/immunosuppressive-myeloid-cells-blockade-in-the-glioma-microenvironment-enhances-the-efficacy-of-immune-stimulatory-gene-therapy
#11
Neha Kamran, Padma Kadiyala, Meghna Saxena, Marianela Candolfi, Youping Li, Mariela A Moreno-Ayala, Nicholas Raja, Diana Shah, Pedro R Lowenstein, Maria G Castro
Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. It is therefore imperative to develop multipronged approaches when aiming to generate a robust anti-tumor immune response. Herein, we tested whether combining MDSC depletion or checkpoint blockade would augment the efficacy of immune-stimulatory herpes simplex type-I thymidine kinase (TK) plus Fms-like tyrosine kinase ligand (Flt3L)-mediated immune stimulatory gene therapy...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28122590/pd-1-pd-l1-b7-h1-and-tumor-site-immune-modulation-therapy-the-historical-perspective
#12
REVIEW
Jun Wang, Ruirong Yuan, Wenru Song, Jingwei Sun, Delong Liu, Zihai Li
The current success of targeted inhibition against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1/Programmed Death Ligand 1 (PD-1/PD-L1, herein collectively referred to as PD) pathways is hailed as a cancer immunotherapy breakthrough. PD-L1, known also as B7 homolog 1 (B7-H1), was initially discovered by Dr. Lieping Chen in 1999. To recognize the seminal contributions by Chen to the development of PD-directed therapy against cancer, the Chinese American Hematologist and Oncologist Network (CAHON) decided to honor him with its inaugural Lifetime Achievement Award in Hematology and Oncology at the CAHON's 2015 annual meeting...
January 25, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28122336/distinct-patterns-of-infiltrating-cd8-t-cells-in-hpv-and-cd68-macrophages-in-hpv-oropharyngeal-squamous-cell-carcinomas-are-associated-with-better-clinical-outcome-but-pd-l1-expression-is-not-prognostic
#13
Kenneth Oguejiofor, Henry Galletta-Williams, Simon J Dovedi, Darren L Roberts, Peter L Stern, Catharine M L West
Immunotherapies are beginning to revolutionise treatment paradigms in oncology with monoclonal antibodies (mAb) targeting T-cell co-inhibitory (e.g. PD-1/PD-L1) and co-stimulatory pathways (e.g. CTLA-4/CD28) demonstrating clinical utility. Some clinical studies demonstrate that responsiveness to PD-1/PD-L1 mAb therapy is greater in patients with expression of PD-L1 in the tumour microenvironment. However, robust responses have also been observed in patients with low or absent expression of PD-L1. Using multiplex immuno-fluorescent labelling we sought to determine how infiltration of tumours by CD8+ T-cells, their expression of PD-1, and the expression of PD-L1 on both tumours and CD68 cells (macrophages) correlated with HPV status and outcome in a cohort of 124 oropharyngeal squamous cell carcinomas (OPSCC)...
January 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28116090/erratum-to-a-case-report-of-grover-s-disease-from-immunotherapy-a-skin-toxicity-induced-by-inhibition-of-ctla-4-but-not-pd-1
#14
Marc Uemura, Faisal Fa'ak, Cara Haymaker, Natalie McQuail, Elizabeth Sirmans, Courtney W Hudgens, Lydia Barbara, Chantale Bernatchez, Jonathan L Curry, Patrick Hwu, Michael T Tetzlaff, Adi Diab
[This corrects the article DOI: 10.1186/s40425-016-0157-6.].
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28114249/inhibitors-of-cytotoxic-t-lymphocyte-antigen-4-and-programmed-death-1-programmed-death-1-ligand-for-metastatic-melanoma-dual-versus-monotherapy-summary-of-advances-and-future-directions-for-studying-these-drugs
#15
Kimberly Loo, Adil I Daud
Immense progress in the field of cancer immunotherapy has garnered several novel and successful treatments for metastatic melanoma. Beginning with therapies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), objective response rates, overall survival, and long-term survival were significantly increased when compared with glycoprotein 100 vaccine therapies. Expanding the breadth of therapies aimed to "release the breaks" on the active immune system, anti-programmed death 1 (PD-1) and anti-programmed death 1 ligand (PD-L1) therapies further improved overall survival, progression-free survival, and objective tumor response while exhibiting more favorable safety profiles compared with ipilimumab and to chemotherapy agents...
January 2017: Cancer Journal
https://www.readbyqxmd.com/read/28111041/-tissue-biomarkers-of-response-to-anti-pd-1-immunotherapies-in-melanoma
#16
Julien Adam, Gorana Tomasic, Caroline Robert
Prognosis and treatment of advanced melanoma have been transformed by the success of immunotherapies, in particular agents targeting PD-1. PD-L1 expression assessed by immunohistochemistry in not an effective predictive biomarker to select patients in this tumor type, since significant clinical benefit was observed in the group of patients with negative tumors. The predictive value of PD-L1 testing to select patients for combination of anti-PD-1 and anti-CTLA-4 agents is under evaluation. Other tissue biomarkers are emerging to identify sensitive tumors to anti-PD-1 agents...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#17
REVIEW
C Alberti
Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation...
September 2017: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#18
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28093620/inflammatory-bowel-disease-and-cancer-response-due-to-anti-ctla-4-is-it-in-the-flora
#19
REVIEW
Franck Carbonnel, Emilie Soularue, Clélia Coutzac, Nathalie Chaput, Christine Mateus, Patricia Lepage, Caroline Robert
Checkpoint inhibitors blocking CTLA-4 (ipilimumab) and PD-1 (nivolumab, pembrolizumab) have transfigured our cancer treatment paradigm. However, these drugs can induce immune-related adverse events that share clinical and pathological characteristics with immune-mediated diseases. One of the most severe immune-related adverse event observed with anti-CTLA-4 is an enterocolitis that mirrors naturally occurring inflammatory bowel disease. This paper reviews the clinical, immunological, and microbiota data associated with the immune-related enterocolitis induced by the cancer immunotherapy blocking CTLA-4, ipilimumab...
January 16, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28076863/adverse-renal-effects-of-immune-checkpoint-inhibitors-a-narrative-review
#20
Rimda Wanchoo, Sabine Karam, Nupur N Uppal, Valerie S Barta, Gilbert Deray, Craig Devoe, Vincent Launay-Vacher, Kenar D Jhaveri
BACKGROUND: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. SUMMARY: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity...
2017: American Journal of Nephrology
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