Current opinion in investigational drugs最新文献

Anti-GITR antibodies--potential clinical applications for tumor immunotherapy. 抗gitr抗体——肿瘤免疫治疗的潜在临床应用

Current opinion in investigational drugs Pub Date : 2010-12-01

David A Schaer, Adam D Cohen, Jedd D Wolchok

{"title":"Anti-GITR antibodies--potential clinical applications for tumor immunotherapy.","authors":"David A Schaer, Adam D Cohen, Jedd D Wolchok","doi":"","DOIUrl":"","url":null,"abstract":"Since the development of the first vaccines, modern medicine has been consistently aiming to improve the efficacy of immune responses. Traditionally, adjuvants have been used as non-specific immune modulators to enhance recognition and activation against a desired antigen. By providing 'danger' signals to the immune system, adjuvants activate innate immunity, which enhances the development of protective and therapeutic adaptive immune responses. The newest class of immune modulators bypasses the innate response and targets cells of the adaptive response directly. Targeted immunomodulatory therapy is focused primarily on the activation of costimulatory receptors (eg, 4-1BB, OX40 and GITR [glucocorticoid-induced TNF receptor-related gene]) or the blockade of co-inhibitory receptors (eg, CTLA-4, PD-1 and PD-L1) on T-cells during activation and/or effector responses. With promising clinical results obtained to date, immunomodulatory therapy is becoming an integral part of immunotherapeutic approaches. The modulation of GITR is listed as one of the top 25 most promising research areas by the NCI, and has demonstrated potential in both antitumor and vaccine settings. This review discusses the role of GITR as a potential target for immunomodulatory therapy, as well as the research involved in understanding the mechanisms of anti-GITR therapy and current progress in translation into the clinic.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":" ","pages":"1378-86"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New approaches to the development of adenoviral dendritic cell vaccines in melanoma. 开发黑色素瘤腺病毒树突状细胞疫苗的新方法。

Current opinion in investigational drugs Pub Date : 2010-12-01

Lisa H Butterfield, Lazar Vujanovic

引用次数: 0

Necitumumab, a fully human IgG1 mAb directed against the EGFR for the potential treatment of cancer. Necitumumab，一种针对EGFR的全人IgG1单抗，用于潜在的癌症治疗。

Current opinion in investigational drugs Pub Date : 2010-12-01

Rodrigo Dienstmann, Josep Tabernero

{"title":"Necitumumab, a fully human IgG1 mAb directed against the EGFR for the potential treatment of cancer.","authors":"Rodrigo Dienstmann, Josep Tabernero","doi":"","DOIUrl":"","url":null,"abstract":"Necitumumab (IMC-11F8), under development by ImClone Systems in collaboration with Bristol-Myers Squibb, is a fully human IgG1 mAb targeting the epidermal growth factor receptor (EGFR), for the potential intravenous treatment of cancer, in particular NSCLC. In vitro studies demonstrate that necitumumab inhibits downstream targets in the EGFR pathway (eg, MAPK), which are important for cellular proliferation, differentiation, invasion and metastasis. Furthermore, because necitumumab is an IgG1 construct, it has the potential to induce antibody-dependent cell-mediated cytotoxicity against tumor cells. Preclinical studies indicated that the antitumor activity of necitumumab is either comparable with or superior to that of ImClone's chimeric anti-EGFR mAb cetuximab. In a phase I clinical trial in patients with advanced solid malignancies, necitumumab displayed nonlinear pharmacokinetic behavior. The toxicity profile of necitumumab is acceptable, with skin toxicity being the most frequently reported adverse event in the phase I and II clinical trials conducted to date. Preliminary data from a phase II clinical trial of necitumumab in combination with chemotherapy for the first-line treatment of advanced colon cancer are promising. Success in the ongoing phase III clinical trials in patients with advanced NSCLC would lead to necitumumab becoming a valuable addition to future therapeutic strategies in oncology.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":" ","pages":"1434-41"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracellular amino acid sensing and mTORC1-regulated growth: new ways to block an old target? 细胞内氨基酸传感和mtorc1调控的生长:阻断旧靶点的新方法?

Current opinion in investigational drugs Pub Date : 2010-12-01

Deborah C I Goberdhan

{"title":"Intracellular amino acid sensing and mTORC1-regulated growth: new ways to block an old target?","authors":"Deborah C I Goberdhan","doi":"","DOIUrl":"","url":null,"abstract":"Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a multicomponent, nutrient-sensitive protein that is implicated in a wide range of major human diseases. mTORC1 responds to both growth factors and changes in local amino acid levels. Until recently, the intracellular amino acid-sensing mechanism that regulates mTORC1 had remained unexplored. However, studies in human cells in culture have demonstrated that in response to amino acid stimulation, mTOR (a conserved member of the PI3K superfamily) is shuttled to late endosomal and lysosomal compartments, where it binds the Ragulator-Rag complex and is assembled into active mTORC1. Members of the proton-assisted amino acid transporter (PAT/SLC36) family have been identified as critical components of the amino acid-sensing system that regulates mTORC1 present in endosomal and lysosomal membranes. These discoveries not only highlight several new potential drug targets that could impact selectively on mTORC1 activity in cancer cells, but also provide novel insights into the strategies used by such cells to outcompete their neighbors in growth factor- and nutrient-depleted conditions. In this review, recent mechanistic insights into how mTORC1 activity is controlled by amino acids and the potential for the selective targeting this regulatory input are discussed.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":" ","pages":"1360-7"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044466/pdf/ukmss-33865.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene therapy for HCV/HBV-induced hepatocellular carcinoma. HCV/ hbv诱导的肝细胞癌的基因治疗

Current opinion in investigational drugs Pub Date : 2010-12-01

Cristian Smerdou, Stephan Menne, Ruben Hernandez-Alcoceba, Gloria Gonzalez-Aseguinolaza

{"title":"Gene therapy for HCV/HBV-induced hepatocellular carcinoma.","authors":"Cristian Smerdou, Stephan Menne, Ruben Hernandez-Alcoceba, Gloria Gonzalez-Aseguinolaza","doi":"","DOIUrl":"","url":null,"abstract":"Infection with HBV and HCV are considered the most important etiological factors for hepatocellular carcinoma (HCC). Current treatment options are insufficient, creating an urgent need for new therapeutic strategies that inhibit disease progression and improve survival in patients with HCC. A promising strategy for the treatment of HCC is gene therapy (GT), which is characterized by the transduction of tumor cells with genes displaying antitumor properties, such as pro-apoptotic, suicide, anti-angiogenic and immunomodulatory genes, as well as siRNAs. Other GT strategies have investigated oncolytic viral vectors that propagate specifically in tumor cells and, subsequently, kill these malignant cells. Furthermore, GT strategies directed toward halting virus proliferation, such as genetic vaccines or genetic interference with viral replication, as well as strategies that prevent viral induced pre-carcinogenic changes, represent the most efficient strategies to prevent HCC development. These GT approaches are promising alternatives to, and could complement or substitute, current treatment options for HCC. This review summarizes trends in GT during the past decade, including investigations in animal models and patients for the prevention and treatment of hepatitis virus-induced HCC.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":" ","pages":"1368-77"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Agents targeting the Hedgehog pathway for pancreatic cancer treatment. 靶向Hedgehog通路治疗胰腺癌的药物。

Current opinion in investigational drugs Pub Date : 2010-12-01

Savita Bisht, Peter Brossart, Anirban Maitra, Georg Feldmann

引用次数: 0

The antifolates: evolution, new agents in the clinic, and how targeting delivery via specific membrane transporters is driving the development of a next generation of folate analogs. 抗叶酸药物:进化，临床中的新药物，以及如何通过特定的膜转运蛋白靶向递送正在推动下一代叶酸类似物的发展。

Current opinion in investigational drugs Pub Date : 2010-12-01

I David Goldman, Shrikanta Chattopadhyay, Rongbao Zhao, Richard Moran

引用次数: 0

Pharmacological inhibition of TGFβ as a strategy to augment the antitumor immune response. 药理抑制TGFβ作为增强抗肿瘤免疫反应的策略。

Current opinion in investigational drugs Pub Date : 2010-12-01

Brent A Hanks, Michael A Morse

引用次数: 0

Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer. 阻断PD1通路的单克隆抗体作为癌症免疫疗法的临床进展。

Current opinion in investigational drugs Pub Date : 2010-12-01

Justin Kline, Thomas F Gajewski

引用次数: 0

Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases. 克唑替尼，c-Met和ALK受体酪氨酸激酶的小分子双重抑制剂。

Current opinion in investigational drugs Pub Date : 2010-12-01

Scott J Rodig, Geoffrey I Shapiro

{"title":"Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases.","authors":"Scott J Rodig, Geoffrey I Shapiro","doi":"","DOIUrl":"","url":null,"abstract":"Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival. Since the first published characterizations of crizotinib only a few years ago, the drug has been extensively validated as a highly specific inhibitor of c-Met and ALK among > 120 different RTKs surveyed. In preclinical tumor xenograft studies, crizotinib inhibited the growth and survival of cell lines dependent upon c-Met or ALK enzymatic activity. Crizotinib has been particularly effective against anaplastic large cell lymphoma and non-small cell lung cancer (NSCLC) cell lines that harbor ALK translocations resulting in expression of oncogenic ALK fusion proteins. During early-stage clinical testing, crizotinib was well tolerated and produced dramatic antitumor activity in patients with ALK-rearranged NSCLC. At the time of publication, an ongoing phase III clinical trial is comparing crizotinib with standard second-line chemotherapy in previously treated patients with NSCLC harboring ALK rearrangement, and a phase III trial comparing crizotinib with standard chemotherapy in the first-line setting in non-squamous lung cancer is planned. Thus, in the future, crizotinib is expected to become a highly used therapeutic for the treatment of ALK-rearranged tumors.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":" ","pages":"1477-90"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29533179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0