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Daniel P Petrylak, Thomas Powles, Joaquim Bellmunt, Fadi Braiteh, Yohann Loriot, Rafael Morales-Barrera, Howard A Burris, Joseph W Kim, Beiying Ding, Constanze Kaiser, Marcella Fassò, Carol O'Hear, Nicholas J Vogelzang
Importance: Atezolizumab (anti-programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. Objective: To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. Design, Setting, and Participants: Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study...
April 1, 2018: JAMA Oncology
Romualdo Barroso-Sousa, William T Barry, Ana C Garrido-Castro, F Stephen Hodi, Le Min, Ian E Krop, Sara M Tolaney
Importance: If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown. Objective: To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens. Data Sources: A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase...
February 1, 2018: JAMA Oncology
Brant A Inman, Thomas A Longo, Sundhar Ramalingam, Michael R Harrison
Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses...
April 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yi Zheng, Yicheng Yang, Shu Wu, Yongqiang Zhu, Xiaolong Tang, Xiaopeng Liu
As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated...
July 4, 2017: Bioengineered
Guo-Wu Zhou, Ye Xiong, Si Chen, Fan Xia, Qiang Li, Jia Hu
BACKGROUND: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC...
August 2016: Medicine (Baltimore)
Lajos Pusztai, Andrea Ladányi, Borbála Székely, Magdolna Dank
The prognostic value of tumor infiltrating lymphocytes in breast cancer has long been recognized by histopathologists. These observations were reaffirmed by recent immunohistochemistry and gene expression profiling studies that also revealed an association between greater chemotherapy sensitivity and extensive lymphocytic infiltration in early stage breast cancers treated with neoadjuvant chemotherapy. These results suggest that local anti-tumor immune response can at least partially control cancer growth and may mediate the antitumor effects of chemotherapy...
March 2, 2016: Magyar Onkologia
Rong Deng, Daniela Bumbaca, Cinthia V Pastuskovas, C Andrew Boswell, David West, Kyra J Cowan, Henry Chiu, Jacqueline McBride, Clarissa Johnson, Yan Xin, Hartmut Koeppen, Maya Leabman, Suhasini Iyer
MPDL3280A is a human monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), and exerts anti-tumor activity mainly by blocking PD-L1 interaction with programmed cell death-1 (PD-1) and B7.1. It is being investigated as a potential therapy for locally advanced or metastatic malignancies. The purpose of the study reported here was to characterize the pharmacokinetics, pharmacodynamics, tissue distribution and tumor penetration of MPDL3280A and/or a chimeric anti-PD-L1 antibody PRO304397 to help further clinical development...
2016: MAbs
Julian Swatler, Ewa Kozłowska
Tumor cells may express on their surface various characteristic antigens that can induce antitumor immunity. However, cancer in human body may induce an immunosuppressive microenvironment that limits immune response to its antigens. For many years scientists have tried to develop an immunotherapy which would induce a potent antitumor immune response and lead to an elimination of the disease. One of the most promising immunotherapies is blockade of immune checkpoints, i.e. a group of costimulatory molecules negatively regulating the immune system...
January 26, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Samit Chatterjee, Wojciech G Lesniak, Matthew Gabrielson, Ala Lisok, Bryan Wharram, Polina Sysa-Shah, Babak Behnam Azad, Martin G Pomper, Sridhar Nimmagadda
Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A...
March 1, 2016: Oncotarget
David F McDermott, Jeffrey A Sosman, Mario Sznol, Christophe Massard, Michael S Gordon, Omid Hamid, John D Powderly, Jeffrey R Infante, Marcella Fassò, Yan V Wang, Wei Zou, Priti S Hegde, Gregg D Fine, Thomas Powles
PURPOSE: The objective was to determine the safety and clinical activity of atezolizumab (MPDL3280A), a humanized programmed death-ligand 1 (PD-L1) antibody, in renal cell carcinoma (RCC). Exploratory biomarkers were analyzed and associated with outcomes. PATIENTS AND METHODS: Seventy patients with metastatic RCC, including clear cell (ccRCC; n = 63) and non-clear cell (ncc; n = 7) histologies, received atezolizumab intravenously every 3 weeks. PD-L1 expression was scored at four diagnostic levels (0/1/2/3) that were based on PD-L1 staining on tumor cells and tumor-infiltrating immune cells (IC) with the SP142 assay...
March 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Joan Minguet, Katherine H Smith, Peter Bramlage
Non-small cell lung cancer (NSCLC) is one of the most deadly cancers worldwide, with poor prognosis once the disease has progressed past the point at which surgery is a viable option. Whilst chemotherapy has improved survival over recent decades, there is still great need for improvements in treatments for patients with advanced disease. Over the last decade, a variety of such drugs have received market approval for treating NSCLC, with a variety of others in the pipeline. Here, we review the development of targeted therapies for the treatment of advanced or metastatic NSCLC, including those already in clinical practice and those in early trials...
June 1, 2016: International Journal of Cancer. Journal International du Cancer
Edward B Garon
In non-small cell lung cancer (NSCLC), the first immune checkpoint inhibitor to be approved by the US Food and Drug Administration was nivolumab, based on a survival advantage over docetaxel in recurrent squamous NSCLC, a difficult-to-treat histology. In addition, several other immune checkpoint inhibitors are also in late-stage development. Most of these agents inhibit the programmed cell death protein 1 (PD-1) pathway, targeting either the PD-1 receptor or its ligand, programmed cell death ligand 1 (PD-L1)...
October 2015: Seminars in Oncology
Christoph Oing, Michael Rink, Karin Oechsle, Christoph Seidel, Gunhild von Amsberg, Carsten Bokemeyer
PURPOSE: We comprehensively reviewed current efforts and advances in the field of chemotherapeutic and biologically targeted treatment options after the failure of cisplatin based, first line regimens for urothelial carcinoma. MATERIALS AND METHODS: We searched MEDLINE®, Central®, and meeting abstracts of ASCO (American Society of Clinical Oncology) and ESMO (European Society for Medical Oncology) to identify original articles, reviews and retrospective analyses on second line treatment of urothelial carcinoma...
February 2016: Journal of Urology
Sam S Chang
No abstract text is available yet for this article.
October 2015: Journal of Urology
Eléonore de Guillebon, Pauline Roussille, Eric Frouin, David Tougeron
Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1 (PD-1) and program death-ligand 1 (PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies (mAbs), called immune checkpoint inhibitors (ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment...
August 15, 2015: World Journal of Gastrointestinal Oncology
Luisa Carbognin, Sara Pilotto, Michele Milella, Vanja Vaccaro, Matteo Brunelli, Anna Caliò, Federica Cuppone, Isabella Sperduti, Diana Giannarelli, Marco Chilosi, Vincenzo Bronte, Aldo Scarpa, Emilio Bria, Giampaolo Tortora
BACKGROUND: The potential predictive role of programmed death-ligand-1 (PD-L1) expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research. METHODS: Overall response rate (ORR) was extracted from phase I-III trials investigating nivolumab, pembrolizumab and MPDL3280A for advanced melanoma, non-small cell lung cancer (NSCLC) and genitourinary cancer, and cumulated by adopting a fixed and random-effect model with 95% confidence interval (CI)...
2015: PloS One
Joel Sunshine, Janis M Taube
Tumors may adopt normal physiologic checkpoints for immunomodulation leading to an imbalance between tumor growth and host surveillance. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host-tumor interaction. Nivolumab and pembrolizumab are the anti-PD-1 antibodies that are currently the furthest in clinical development, and anti-PD-L1 agents under investigation include MPDL3280A, MEDI4736, and BMS-936559. These agents have been used to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin lymphoma, amongst other tumor types...
August 2015: Current Opinion in Pharmacology
Ashley Cimino-Mathews, Jeremy B Foote, Leisha A Emens
The immune system is active in breast cancer, playing a dual role in tumor progression and in immune surveillance. Infiltrating immune cells are both prognostic and predictive of response to standard breast cancer therapies. Breast cancer vaccines can activate and expand tumor-specific T cells, but have enjoyed minimal clinical success to date. Immune checkpoint blockade is a new approach to cancer immunotherapy, with documented clinical responses in diverse tumor types. Interest in breast cancer immunotherapy has been reignited by recent reports of objective responses in metastatic triple-negative breast cancer with both pembrolizumab (a programmed cell death protein 1 [PD-1] antagonist) and MPDL3280A (a programmed cell death ligand 1 [PD-L1] antagonist)...
May 2015: Oncology (Williston Park, NY)
Edward Cha, Jeffrey Wallin, Marcin Kowanetz
Cancer immunotherapy has become a popular anticancer approach, with the goal of stimulating immune responses against tumor cells. Recent evidence has demonstrated that the use of monoclonal antibodies targeting the programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) checkpoint pathway can result in well-tolerated clinical responses in a wide variety of tumor types. This review summarizes the safety, clinical activity and biomarker data for the anti-PD-L1 antibody, MPDL3280A, from a phase Ia multicenter, dose-escalation and -expansion trial...
June 2015: Seminars in Oncology
Yide Huang, Shu-Dong Zhang, Cian McCrudden, Kwok-Wah Chan, Yao Lin, Hang-Fai Kwok
Immunotherapy is a promising strategy for the treatment of various types of cancer. An antibody that targets programmed death ligand-1 (PD-L1) pathway has been shown to be active towards various types of cancer, including melanoma and lung cancer. MPDL3280A, an anti-PD-L1 antibody, has shown clear clinical activity in PD-L1-overexpressing bladder cancer with an objective response rate of 40-50%, resulting in a breakthrough therapy designation granted by FDA. These events pronounce the importance of targeting the PD-L1 pathway in the treatment of bladder cancer...
June 2015: Oncology Reports
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