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immune check point inhibitor

C Genova, A Alama, S Coco, E Rijavec, M G Dal Bello, I Vanni, F Biello, G Barletta, G Rossi, F Grossi
Vinflunine belongs to the class of vinca alkaloids and acts by disrupting the microtubule dynamics during cell cycle; this agent is currently available for previously treated advanced transitional cell carcinoma in Europe. The aim of this invited review is to evaluate the potential role of vinflunine for the treatment of non-small cell lung cancer (NSCLC). Areas covered: The potential role of vinflunine in NSCLC is discussed on the basis of the available data, including full papers and meeting abstracts. Relevant preclinical studies describing the pharmacological properties of vinflunine are also included...
October 22, 2016: Expert Opinion on Investigational Drugs
Masatoshi Kudo
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Sonazoid-enhanced ultrasound and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI are the most important imaging modalities in diagnosing HCC. There are 2 non-contradictory HCC treatment algorithms in Japan. Hepatic arterial infusion chemotherapy plays an important role in the treatment of advanced HCC with main or branch portal vein invasion. Regorafenib, as a second-line systemic treatment, prolongs survival in patients with intermediate and advanced HCC who progressed on sorafenib...
2016: Digestive Diseases
Marinos Tsiatas, Giannis Mountzios, Giuseppe Curigliano
The advent of immunotherapy has transformed the treatment paradigm of several solid tumors and is expected to influence the therapeutic algorithm even more in the future following the results of numerous ongoing clinical trials in a wide range of malignancies. Exploiting the anti-cancer effect of the immune system with the use of vaccines, viral vectors, and more lately with immune check-point inhibitors and chimeric antigen receptor modification, has been proven a successful therapeutic strategy in a broad spectrum of tumors...
July 2016: Annals of Translational Medicine
Francesca De Felice, Daniela Musio, Raffaele Cassese, Giovanni Luca Gravina, Vincenzo Tombolini
BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent brain tumor. Despite recent advances in treatment approaches the prognosis remains poor, with a median overall survival of 14.6 months. Immunotherapy is the subject of ongoing research and its benefit is becoming evident in other malignancies. Immune check-points such as cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed cell death receptor (PD-1) and indoleamine 2,3-dioxygenase (IDO) reduce immune response. OBJECTIVE: To clarify the role of immune check point inhibitors in GBM management...
August 13, 2016: Current Cancer Drug Targets
Alessandro D Santin, Stefania Bellone, Natalia Buza, Jungmin Choi, Peter E Schwartz, Joseph Schlessinger, Richard P Lifton
PURPOSE: The management of endometrial carcinoma no longer amenable to treatment with surgery or radiation has not improved significantly with modern chemotherapy. Alternative therapeutic options are desperately needed. EXPERIMENTAL DESIGN: We describe 2 heavily pretreated patients with recurrent disease refractory to surgery, radiation and chemotherapy treated with the anti-PD1 immune check-point inhibitor nivolumab. RESULTS: Patient # 1 harbored an ultra-mutated (Mutation Load/MB = 117...
August 2, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Flavia Fontana, Dongfei Liu, Jouni Hirvonen, Hélder A Santos
The application of nanotechnology to the treatment of cancer or other diseases has been boosted during the last decades due to the possibility to precise deliver drugs where needed, enabling a decrease in the drug's side effects. Nanocarriers are particularly valuable for potentiating the simultaneous co-delivery of multiple drugs in the same particle for the treatment of heavily burdening diseases like cancer. Immunotherapy represents a new concept in the treatment of cancer and has shown outstanding results in patients treated with check-point inhibitors...
July 29, 2016: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
Elizabeth Dudnik, Shlomit Yust-Katz, Hovav Nechushtan, Daniel A Goldstein, Alona Zer, Dov Flex, Tali Siegal, Nir Peled
Central nervous system (CNS) metastases occur in 30% of patients with advanced non-small cell lung cancer (NSCLC). Localized treatments targeting CNS metastases result in delays in systemic therapy administration and are associated with neurocognitive impairment. Nivolumab is an immune check-point inhibitor that is approved as a second-line treatment of NSCLC. Data regarding the intracranial activity of nivolumab is lacking. We retrospectively reviewed the efficacy and safety of nivolumab in five patients with advanced NSCLC and new/progressing intracranial metastases...
August 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Takumi Sugimoto, Takashi Watanabe
The microenvironment of follicular lymphoma (FL) is composed of tumor-infiltrating CD8(+) T cells, follicular regulatory T cells, lymphoma-associated macrophages and mast cells, follicular helper T cells, follicular dendritic cells, and follicular reticular cells, all of which have been reported to have relevance in the prognosis of FL patients. In addition, some of these cells play a role in the histologic transformation of FL. Macrophages contribute to a poor prognosis in FL patients treated in the pre-rituximab era, but are associated with good prognosis in those treated in the rituximab era...
2016: Journal of Clinical and Experimental Hematopathology: JCEH
Seongseok Yun, Nicole D Vincelette, Myke R Green, Andrea E Wahner Hendrickson, Ivo Abraham
Anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) inhibitors have been shown to significantly improve survival in patients with metastatic cutaneous melanoma. However, there was some heterogeneity as well as some variation in the degree of benefit across studies. We reviewed randomized trials and performed a meta-analysis to determine the efficacy and safety of immune checkpoint inhibitors in comparison with conventional regimens. Eligible studies were limited to randomized controlled trials comparing anti-CTLA-4 or anti-PD-1 inhibitors to chemotherapy or vaccination treatment in adult patients with unresectable cutaneous metastatic melanoma...
July 2016: Cancer Medicine
Marlana Orloff, Ryan Weight, Matias E Valsecchi, Takami Sato
The combination of immune checkpoint inhibitors ipilimumab and nivolumab has been recently been FDA approved for first line treatment of unresectable and metastatic BRAF wild type melanoma. The approval came following the impressive results of the CheckMate 067, where the combination of ipilimumab and nivolumab appeared to outperform each as a single agent in regards to response rate and progression free survival. Though we await final overall survival data, the combination will likely be adapted by many oncologists and integrated into the ever changing melanoma treatment algorithm...
2016: Reviews on Recent Clinical Trials
Nicola Hardwick, Paul H Frankel, Mihaela Cristea
The immune system plays an active role in the pathogenesis of ovarian cancer (OC), as well as in the mechanisms of disease progression and overall survival (OS). Immunotherapy in gynecological cancers could help to revert immunosuppression and lymphocyte depletion due to prior treatments. Current immunotherapies for ovarian cancer, like all cancer immunotherapy, are based on either stimulating the immune system or reverting immune suppression. Several approaches have been used, including therapeutic vaccines, monoclonal antibodies; checkpoint inhibitors and adoptive T cell transfer...
March 2016: Current Treatment Options in Oncology
Xiao-Na Fang, Li-Wu Fu
Inhibitors of immune check-point molecule, programmed cell death 1 (PD-1) and its ligand, programmed cell death ligand 1 (PD-L1) have attracted much attention in cancer immunotherapy recently due to their durable antitumor effects in various malignances, especially the advanced ones. Unfortunately, only a fraction of patients with advanced tumors could benefit from anti-PD-1/PD-L1 therapy, while others still worsened. The key to this point is that there are no efficient biomarkers for screening anti-PD-1/PD-L1-sensitive patients...
2016: Recent Patents on Anti-cancer Drug Discovery
Gabriel A Rivera, Iman Saramipoor Behbahan, Peter L Greenberg
Immunologic tolerance to cancer has recently been shown to have major implications for the ability of tumors to survive despite a variety of therapeutic approaches. A critical mechanism underlying this microenvironment dysfunction relates to the ability of tumor cells to block immune check points through expression of specific proteins that interfere with immune cell effector function. Recent advances based on this model have led translational work showing therapeutic efficacy in a variety of solid and lymphoid tumors...
May 2016: Leukemia & Lymphoma
Omar Abdel-Rahman, Hesham ElHalawani, Mona Fouad
BACKGROUND: We performed a meta-analysis of the risk of endocrine adverse events associated with immune check point inhibitors. METHODS: Eligible studies included randomized trials of cancer patients on immune checkpoint inhibitors; describing events of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency. RESULTS: A total of ten clinical trials were eligible for the meta-analysis. The relative risk of all-grade hypothyroidism, hyperthyroidism, hypophyisitis and adrenal insufficiency were 8...
February 2016: Future Oncology
V Bajčiová
BACKGROUND: Currently, most children with cancer can be cured with standard therapy (surgery, chemotherapy, radiotherapy). The only limiting factor is its severe acute toxicity and late adverse events. In pediatric oncology, immunotherapy has been delayed but the initial clinical trials of immunotherapy show a good tolerance and promising results, especially in the setting of refractory or recurrent high-risk tumors. In this article, we will discuss a current situation in pediatric oncology, what immunotherapies are being tested in the clinical practice, from monoclonal antibodies, check- point inhibitors to tumor vaccines, T-lymphocytes with chimeric antigen receptors, cytokines and innate immunity...
2015: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
B Říhová, M Šťastný
Immunotherapy dates back to 1868 when German physicist Busch intentionally infected patients suffering from soft tissue sarcoma with erysipelas. Rapid tumor shrinkage was observed but response was only partial and tumor recurrence subsequently occurred. It was William B. Coley who in 1891 injected a patient with a soft tissue sarcoma with streptococcal cultures. Following a severe attack of erysipelas, the tumor underwent extensive necrosis and the patient remained diseasefree for eight years. The mixture of Streptococcus and other bacteria including Seratia marcescens, Staphylococcus and Escherichia coli was referred to as Coleys toxin and was used for the next 45 years...
2015: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Brett J Theeler, Mark R Gilbert
Glioblastoma is a refractory malignancy with limited treatment options at tumor recurrence. Only a small proportion of patients survive 2 years or longer with the current standard of care. Gene expression profiling can segregate newly diagnosed patients into groups with different prognoses, and these biomarkers are being incorporated into a new generation of personalized clinical trials. Using the experience from recently completed large scale, multi-faceted, randomized glioblastoma clinical trials, a new clinical trial paradigm is being established to move promising therapies forward into the newly diagnosed treatment setting...
2015: BMC Medicine
Gulden Menderes, Jonathan Black, Carlton L Schwab, Alessandro D Santin
The prognosis of patients with metastatic cervical cancer is poor with a median survival of 8-13 months. Despite the potency of chemotherapeutic drugs, this treatment is rarely curative and should be considered palliative only. In the last few years, a better understanding of Human papillomavirus tumor-host immune system interactions and the development of new therapeutics targeting immune check points have renewed interest in the use of immunotherapy in cervical cancer patients. Moreover, next generation sequencing has emerged as an attractive option for the identification of actionable driver mutations and other markers...
2016: Expert Review of Anticancer Therapy
Carlo Genova, Erika Rijavec, Francesco Grossi
Squamous non-small cell lung cancer (NSCLC) has always been characterized by a limited number of therapeutic options and by the lack of actionable biomarkers compared to its non-squamous counterpart. Recent clinical trials have led to the approval of new anti-neoplastic drugs available to both non-squamous and squamous NSCLC, consisting in a vascular-disrupting agent and two immune check-point inhibitors; additionally, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) is currently under evaluation by the Food and Drug Administration (FDA)...
2016: Expert Review of Anticancer Therapy
Divaya Bhutani, Lawrence G Lum
PURPOSE OF REVIEW: Adoptive T-cell therapy has become one of the most exciting fields of cancer therapy in the past few years. In this article, we describe a method which combines adoptive T-cell therapy with antibody therapy by arming T cells from cord blood, normal patients, and cancer patients with bispecific antibodies capable of binding to tumor-associated antigens on one side of the bispecific antibody construct and T cells on another side of the construct. This approach redirects T cells against tumor cells in a non-MHC-restricted manner...
November 2015: Current Opinion in Hematology
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