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monoclonal antibodies in therapy

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https://www.readbyqxmd.com/read/29146721/development-of-a-function-blocking-antibody-against-fibulin-3-as-targeted-reagent-for-glioblastoma
#1
Mohan Sobhana Nandhu, Prajna Behera, Vivek Bhaskaran, Sharon L Longo, Lina M Barrera-Arenas, Sadhak Sengupta, Diego J Rodriguez-Gil, E Antonio Chiocca, Mariano S Viapiano
PURPOSE: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NF-kB signaling. EXPERIMENTAL DESIGN: We used deletion constructs to identify a key signaling motif of fibulin-3. A monoclonal antibody (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3...
November 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29145737/pembrolizumab-as-first-line-therapy-for-metastatic-non-small-cell-lung-cancer
#2
Martin Reck
This review describes trials evaluating the monoclonal antibody pembrolizumab (an immunotherapy that blocks the interaction between programmed death-1 and programmed death-ligand 1 and 2 [PD-L1/PD-L2]) as first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the Phase III KEYNOTE-024 study, pembrolizumab monotherapy significantly improved progression-free survival (primary end point) and overall survival, and was associated with fewer adverse events compared with platinum-based chemotherapy in patients with NSCLC with PD-L1 expression on ≥50% of tumor cells...
November 17, 2017: Immunotherapy
https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#3
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29143289/agents-in-development-for-childhood-acute-lymphoblastic-leukemia
#4
REVIEW
Kelly W Maloney, Lia Gore
Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. Standard chemotherapy has afforded outstanding outcomes for many patients; however, there remain some sub-groups with high-risk features, refractory disease, and patients that  relapse who have a poor prognosis with conventional treatments. Over the past decade, there have been significant advances in newer treatment options, including improved monoclonal antibody therapies, T cell engagers, and chimeric antigen T-cell receptor products, all of which have changed the landscape for patients who relapse...
November 15, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/29143151/next-generation-anti-cd20-monoclonal-antibodies-in-autoimmune-disease-treatment
#5
Fanny Huynh Du, Elizabeth A Mills, Yang Mao-Draayer
The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several autoimmune diseases. The first therapeutic anti-CD20 mAb, rituximab, is a murine-human chimera to which many patients develop antibodies and/or experience infusion-related reactions. A second generation of anti-CD20 mAbs has been designed to be more effective, better tolerated, and of lower immunogenicity. These include the humanized versions: ocrelizumab, obinutuzumab, and veltuzumab, and the fully human, ofatumumab...
November 16, 2017: Auto- Immunity Highlights
https://www.readbyqxmd.com/read/29140271/molecular-targeted-therapies-for-epidermal-growth-factor-receptor-and-its-resistance-mechanisms
#6
REVIEW
Toshimitsu Yamaoka, Motoi Ohba, Tohru Ohmori
Cancer therapies targeting epidermal growth factor receptor (EGFR), such as small-molecule kinase inhibitors and monoclonal antibodies, have been developed as standard therapies for several cancers, such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, breast cancer, and squamous cell carcinoma of the head and neck. Although these therapies can significantly prolong progression-free survival, curative effects are not often achieved because of intrinsic and/or acquired resistance. The resistance mechanisms to EGFR-targeted therapies can be categorized as resistant gene mutations, activation of alternative pathways, phenotypic transformation, and resistance to apoptotic cell death...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29140105/durvalumab-in-non-small-cell-lung-cancer-patients-current-developments
#7
Laura Mezquita, David Planchard
Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population. Durvalumab is under evaluation in early, locally advanced and advanced disease as monotherapy and combined with ICIs, targeted therapies, chemotherapy and radiotherapy...
November 15, 2017: Future Oncology
https://www.readbyqxmd.com/read/29138342/immunotherapy-of-hepatocellular-carcinoma-facts-and-hopes
#8
Mercedes Iñarrairaegui, Ignacio Melero, Bruno Sangro
Treatment of patients with hepatocellular carcinoma in the advanced stage remains a great challenge, with very few drugs approved. After decades of failures of immune therapies, immune checkpoint inhibitors have emerged as potentially effective treatments for patients with hepatocellular carcinoma in the advanced stage. Immune checkpoints, including human cancer, cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), are surface proteins expressed in a variety of immune cells, and mostly provide immunosuppressive signals...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29137309/anti-proliferative-and-pro-apoptotic-effects-induced-by-simultaneous-inactivation-of-her1-and-her2-through-endogenous-polyclonal-antibodies
#9
Narjara González Suárez, Gretchen Bergado Báez, Mabel Cruz Rodríguez, Amelia Gutiérrez Pérez, Lisset Chao García, Diana Rosa Hernández Fernández, Judith Raymond Pous, Belinda Sánchez Ramírez
The human epidermal growth factor receptor (HER1) and its partner HER2 are extensively described oncogenes and validated targets for cancer therapy. However, the effectiveness of monospecific therapies targeting these receptors is hampered by resistance emergence, which is frequently associated with the upregulation of other members of HER family. Combined therapies using monoclonal antibodies or tyrosine kinase inhibitors have been suggested as a promising strategy to circumvent this resistance mechanism. We propose an alternative approach based on simultaneous inactivation of HER1 and HER2 by multi-epitope blockade with specific polyclonal antibodies induced by vaccination...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137301/antitumor-efficacy-of-triple-monoclonal-antibody-inhibition-of-epidermal-growth-factor-receptor-egfr-with-mm151-in-egfr-dependent-and-in-cetuximab-resistant-human-colorectal-cancer-cells
#10
Stefania Napolitano, Giulia Martini, Erika Martinelli, Carminia Maria Della Corte, Floriana Morgillo, Valentina Belli, Claudia Cardone, Nunzia Matrone, Fortunato Ciardiello, Teresa Troiani
Purpose: We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design: MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM151 with irinotecan (induction therapy) followed by MM151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134440/ki67-labeling-index-assessment-and-prognostic-role-in-gastroenteropancreatic-neuroendocrine-neoplasms
#11
REVIEW
Günter Klöppel, Stefano La Rosa
In 1983, a monoclonal antibody, Ki67, was generated, that labeled the nuclei of proliferating non-neoplastic and neoplastic cells. The name Ki67 derived from the city of Kiel (Ki) where the antibody was produced in the university department of pathology and refers to the number of the original clone (67). Systematic assessment of the proliferative activity of tumors using Ki67 started in the 1990s, when Ki67, which only worked on frozen tissue, was complemented by the antibody MIB-1 that also worked in formalin-fixed tissues...
November 13, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29133975/severe-eosinophilic-asthma-from-the-pathogenic-role-of-interleukin-5-to-the-therapeutic-action-of-mepolizumab
#12
REVIEW
Corrado Pelaia, Alessandro Vatrella, Maria Teresa Busceti, Luca Gallelli, Rosa Terracciano, Rocco Savino, Girolamo Pelaia
Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that has been recently approved as an add-on biological treatment for severe eosinophilic asthma, by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Moreover, mepolizumab is also currently included within the step 5 of the Global Initiative for Asthma guidelines, as an add-on therapy for severe uncontrolled asthma. The relevant therapeutic benefits detectable in patients with refractory eosinophilic asthma receiving mepolizumab depend on the pivotal pathogenic role played by IL-5 in these subjects...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29133549/pharmacokinetics-and-exposure-response-analysis-of-rg7667-a-combination-of-two-anti-cytomegalovirus-monoclonal-antibodies-in-a-phase-2a-randomized-trial-to-prevent-cytomegalovirus-infection-in-high-risk-kidney-transplant-recipients
#13
Rong Deng, Yehong Wang, Mauricio Maia, Tracy Burgess, Jacqueline M McBride, X Charlene Liao, Jorge A Tavel, William D Hanley
BACKGROUND: RG7667, a novel combination of two anti-cytomegalovirus (CMV) monoclonal IgG1 antibodies (MCMV5322A and MCMV3068A), was designed to block CMV entry into host cells. It was developed as a potential therapy for preventing CMV infection and disease in transplant recipients. METHODS: In a Phase 2a trial in CMV-seronegative recipients of kidney transplants from CMV-seropositive donors, RG7667 was assessed for preventing CMV infection. Patients received 4 intravenous doses of RG7667 (10 mg/kg of each antibody, n=60) or placebo (n=60) at time of transplant, and 1, 4, and 8 weeks post transplant...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29132419/success-of-anti-cd20-monoclonal-antibody-treatment-for-severe-autoimmune-hemolytic-anemia-caused-by-warm-reactive-immunoglobulin-a-immunoglobulin-g-and-immunoglobulin-m-autoantibodies-in-a-child-a-case-report
#14
Houda Ajmi, Sameh Mabrouk, Saida Hassayoun, Haifa Regaieg, Minyar Tfifha, Chemli Jalel, Hadef Skouri, Noura Zouari, Saoussan Abroug
BACKGROUND: Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects...
November 14, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29132070/sixteen-year-history-of-rituximab-therapy-for-1085-pemphigus-vulgaris-patients-a-systematic-review
#15
REVIEW
Soheil Tavakolpour, HamidReza Mahmoudi, Kamran Balighi, Robabeh Abedini, Maryam Daneshpazhooh
Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin and mucous membranes. Recently, rituximab, a chimeric IgG1 monoclonal antibody which targets the CD20 molecules have been regarded as a promising treatment for PV. In this study, a systematic review was conducted to conclude on how and which PV patients could benefit from rituximab infusion. Search in PubMed results in 114 relevant studies, which met the criteria...
November 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29131413/the-effect-of-epitope-based-ligation-of-icam-1-on-survival-and-retransplantation-of-pig-islets-in-nonhuman-primates
#16
Jae-Il Lee, Jiyeon Kim, Yun-Jung Choi, Hi-Jung Park, Hye-Jin Park, Hae Joo Wi, Sunok Yoon, Jun-Seop Shin, Jin Kyun Park, Kyeong Cheon Jung, Eun Bong Lee, Hee Jung Kang, Eung Soo Hwang, Sang-Joon Kim, Chung-Gyu Park, Seong Hoe Park
BACKGROUND: Pig islet xenotransplantation is a promising alternative to allogeneic transplantation. However, the wide immunologic barrier between pigs and primates limits the long-term survival of the graft. MD-3, a novel monoclonal antibody (mAb) that recognizes a particular epitope of human ICAM-1, can render T cells tolerant to a xenograft by arresting dendritic cell maturation. We report the long-term survival of adult wild-type pig islets and successful retransplantation in nonhuman primates using a protocol comprising induction with MD-3 mAb and maintenance with anti-CD154 mAb and sirolimus...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29131039/adverse-reactions-of-antibody-therapy-for-primary-cutaneous-lymphomas-rituximab-brentuximab-vedotin-alemtuzumab-and-mogamulizumab
#17
I Saulite, E Guenova, W Hoetzenecker
Treatment of advanced PCLs is limited and rarely reaches complete remission despite aggressive treatment modalities, such as polychemotherapy with various adverse effects. However, several monoclonal antibodies drug agents in patients with advanced primary cutaneous lymphomas demonstrate promising efficacy and manageable safety profiles. The monoclonal antibodies drug agents have favourable tolerability compared with multi-agent cytotoxic chemotherapy. However, adverse effects manifest with a broad clinical spectrum, hence the markers of targeted therapies are not limited to tumour cells but found on tumour cells and also on benign T and/or B cells...
2018: Current Problems in Dermatology
https://www.readbyqxmd.com/read/29131036/the-immunogenicity-of-biologic-therapies
#18
Sandra Garcês, Jocelyne Demengeot
Virtually all therapeutic proteins (biologics) elicit an immune response with the consequent production of anti-drug antibodies (ADA). The majority of ADA to therapeutic monoclonal antibodies (mAbs) are directed against the antigen-binding site of the therapeutic mAb, and hence are neutralizing. This nature of the ADA response explains why fully human antibodies can still be highly immunogenic. The detection of ADA is technically challenging and all assays have limitations, namely a limited capacity in detecting ADA in the presence of a drug due to immune complex (IC) formation, which may underestimate the ADA incidence...
2018: Current Problems in Dermatology
https://www.readbyqxmd.com/read/29129443/adjuvant-chemotherapy-with-or-without-bevacizumab-in-patients-with-resected-non-small-cell-lung-cancer-e1505-an-open-label-multicentre-randomised-phase-3-trial
#19
Heather A Wakelee, Suzanne E Dahlberg, Steven M Keller, William J Tester, David R Gandara, Stephen L Graziano, Alex A Adjei, Natasha B Leighl, Seena C Aisner, Jan M Rothman, Jyoti D Patel, Mark D Sborov, Sean R McDermott, Roman Perez-Soler, Anne M Traynor, Charles Butts, Tracey Evans, Atif Shafqat, Andrew E Chapman, Samer S Kasbari, Leora Horn, Suresh S Ramalingam, Joan H Schiller
BACKGROUND: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC. METHODS: We did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC...
November 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29129093/xxxxx
#20
Tomas G Lyons, Geoffrey Y Ku
The poor prognosis for patients with esophagogastric cancers (EGC) requires the development of newer more effective therapies to further improve the treatment outcomes for this disease. Immunotherapy is a novel treatment strategy that is dramatically changing the treatment landscape for several types of cancers. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death the programmed death (PD)-1/PD-ligand are essential immune checkpoint inhibitors that suppress T cell activation. Targeting of these immune checkpoints with monoclonal antibodies has shown clinical efficacy in several solid tumors which has led to their approval and use in routine clinical practice...
October 2017: Chinese Clinical Oncology
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