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      AFM13: a first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy

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      Author(s): , , ,
      Publication date (Electronic):
      Journal: Journal of Hematology & Oncology
      Publisher: BioMed Central

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          Abstract

          Monoclonal antibodies against CD20 molecule have been leading the revolution of lymphoma treatment. In addition to monoclonal antibodies against CD20 and CD30, novel agents of immunotherapeutics in clinical development are being developed and are rapidly migrating to clinical application. One area of active development is NK cell activators, such as AFM13. This review will highlight the latest development of AFM13 as the first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy.

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          The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies

          Li-Li Shi, Shaohua Chen, Lijian Yang … (2013)
          T-cell activation and dysfunction relies on direct and modulated receptors. Based on their functional outcome, co-signaling molecules can be divided as co-stimulators and co-inhibitors, which positively and negatively control the priming, growth, differentiation and functional maturation of a T-cell response. We are beginning to understand the power of co-inhibitors in the context of lymphocyte homeostasis and the pathogenesis of leukemia, which involves several newly described co-inhibitory pathways, including the programmed death-1 (PD-1) and PD-1 ligand (PD-L1) pathway. The aim of this review is to summarize the PD-1 and PD-L1 biological functions and their alterative expression in hematological malignancies. The role of PD-1 and PD-L1 in T-cell immune suppression and the potential for immunotherapy via blocking PD-1 and PD-L1 in hematological malignancies are also reviewed.
          Article 0 comments Cited 127 times – based on 0 reviews     Review now
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            Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics

            Akintunde Akinleye, Parthu Avvaru, Muhammad Furqan … (2013)
            Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate diverse cellular processes including proliferation, adhesion, survival, and motility. Dysregulated PI3K pathway signaling occurs in one-third of human tumors. Aberrantly activated PI3K signaling also confers sensitivity and resistance to conventional therapies. PI3K has been recognized as an attractive molecular target for novel anti-cancer molecules. In the last few years, several classes of potent and selective small molecule PI3K inhibitors have been developed, and at least fifteen compounds have progressed into clinical trials as new anticancer drugs. Among these, idelalisib has advanced to phase III trials in patients with advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma. In this review, we summarized the major molecules of PI3K signaling pathway, and discussed the preclinical models and clinical trials of potent small-molecule PI3K inhibitors.
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              MEK and the inhibitors: from bench to bedside

              Akintunde Akinleye, Muhammad Furqan, Nikhil Mukhi … (2013)
              Four distinct MAP kinase signaling pathways involving 7 MEK enzymes have been identified. MEK1 and MEK2 are the prototype members of MEK family proteins. Several MEK inhibitors are in clinical trials. Trametinib is being evaluated by FDA for the treatment of metastatic melanoma with BRAF V600 mutation. Selumetinib has been studied in combination with docetaxel in phase II randomized trial in previously treated patients with advanced lung cancer. Selumetinib group had better response rate and progression-free survival. This review also summarized new MEK inhibitors in clinical development, including pimasertib, refametinib, PD-0325901, TAK733, MEK162 (ARRY 438162), RO5126766, WX-554, RO4987655 (CH4987655), GDC-0973 (XL518), and AZD8330.
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                Author and article information

                Contributors
                Delong Liu: DELONG_LIU@NYMC.EDU
                Journal
                Journal ID (nlm-ta): J Hematol Oncol
                Journal ID (iso-abbrev): J Hematol Oncol
                Title: Journal of Hematology & Oncology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1756-8722
                Publication date (Electronic): 1 August 2015
                Publication date PMC-release: 1 August 2015
                Publication date Collection: 2015
                Volume: 8
                Electronic Location Identifier: 96
                Affiliations
                [ ]Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
                [ ]Department of Hematology, Shaoxing People’s Hospital, Shaoxing, Zhejiang Province China
                [ ]Division of Hematology & Oncology, New York Medical College, Valhalla, NY 10595 USA
                Article
                Publisher ID: 188
                DOI: 10.1186/s13045-015-0188-3
                PMC ID: 4522136
                PubMed ID: 26231785
                SO-VID: 6b490e58-3505-499a-8fbd-8748a3ed797c
                Copyright © © Wu et al. 2015
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 4 July 2015
                Date accepted : 16 July 2015
                Categories
                Subject: Research Highlight
                Custom metadata
                issue-copyright-statement © The Author(s) 2015

                ScienceOpen disciplines: Oncology & Radiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy

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