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      Recent development in clinical applications of PD-1 and PD-L1 antibodies for cancer immunotherapy

      review-article
      Author(s): 1 , 2 , 2 , , 2 ,
      Publication date (Electronic):
      Journal: Journal of Hematology & Oncology
      Publisher: BioMed Central

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          Abstract

          Antibodies against programmed death (PD) pathway are revolutionizing cancer immunotherapy. Currently five antibodies against PD-1/PD-L1 have been approved. The clinical use of these antibodies is rapidly expanding. Incorporation of PD antibodies into chemotherapy regimens is in active clinical investigations. The combination of pembrolizumab with carboplatin and pemetrexed has been approved for the first line therapy of metastatic non-squamous non-small cell lung cancer. Combination of PD-1/PD-L1 antibodies with small molecule inhibitors such as tyrosine kinase inhibitors and IDO inhibitors are in active clinical trials. This review summarized recent development in clinical trials of PD-1 and PD-L1 antibodies for cancer immunotherapy.

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          Nivolumab for classical Hodgkin lymphoma after autologous stem-cell transplantation and brentuximab vedotin failure: a prospective phase 2 multi-cohort study

          Anas Younes, Armando Santoro, Margaret A. Shipp … (2016)
          Background Malignant cells of classical Hodgkin lymphoma (cHL) are characterised by genetic alterations at the 9p24·1 locus. This leads to overexpression of the programmed death 1 (PD-1) ligands and enables tumour cells to evade immune surveillance. A phase 1b study showed that nivolumab, a PD-1-blocking antibody, produced a high response rate in patients with relapsed and refractory cHL, with an acceptable safety profile. This phase 2 study assessed the clinical benefit of nivolumab monotherapy in patients with cHL after autologous stem-cell transplantation and brentuximab vedotin failure. Methods This ongoing phase 2 study (NCT02181738) assessed the efficacy and safety of nivolumab, administered intravenously over 60 minutes at 3 mg/kg every 2 weeks, in adult patients with cHL who had failed both autologous stem-cell transplantation and brentuximab vedotin. The primary endpoint was objective response rate by independent radiologic review committee (IRRC) assessment. Secondary and other endpoints included duration of response, safety, and assessment of PD-L1 and PD-L2 loci and PD-L1 and PD-L2 protein expression. Findings Among 80 treated patients, the median number of prior therapies was four (range 3–15). With a mean (SD) follow-up of 8·6 months (2·02), objective response rate per IRRC was 66·3% (53/80). The most common drug-related adverse events (≥15%) included fatigue, infusion-related reaction, and rash. The most common drug-related grade 3–4 adverse events were neutropenia and increased lipase levels (both n=4). The most common serious adverse event (any grade) was pyrexia (n=3). Interpretation Nivolumab demonstrated a high response rate and an acceptable safety profile in patients with cHL who progressed following autologous stem-cell transplantation and brentuximab vedotin. Nivolumab may therefore provide a novel treatment option for a patient population with a high unmet need. Ongoing follow-up will help to assess the durability of response. Funding Bristol-Myers Squibb.
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            Incidence of pneumonitis with use of PD-1 and PD-L1 inhibitors in non-small cell lung cancer: A Systematic Review and Meta-analysis of trials.

            Monica Khunger, Sagar Rakshit, Vinay Pasupuleti … (2017)
            PD-1/PD-L1 inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis, and differences according to type of inhibitors and prior chemotherapy use.
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              Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma.

              R Thompson, Haidong Dong, Christine M. Lohse … (2011)
              Release of inhibitory coregulatory proteins into the circulation may represent one mechanism by which tumors thwart immune responses. Our objective was to determine whether soluble B7-H1 (sB7-H1) levels in patients with clear cell renal cell carcinoma (ccRCC) are associated with pathologic features and patient outcome. We developed an ELISA for quantification of sB7-H1 in biological fluids. Biochemical confirmation of the measured analyte as sB7-H1 was done by protein microsequencing using supernates from tumor cell lines. Biological activity of sB7-H1 was assessed in vitro utilizing T-cell apoptosis assays. We tested sB7-H1 levels in the sera from 172 ccRCC patients and correlated sB7-H1 levels with pathologic features and patient outcome. sB7-H1 was detected in the cell supernatants of some B7-H1-positive tumor cell lines. Protein sequencing established that the measured sB7-H1 retained its receptor-binding domain and could deliver proapoptotic signals to T cells. Higher preoperative sB7-H1 levels were associated with larger tumors (P < 0.001), tumors of advanced stage (P = 0.017) and grade (P = 0.044), and tumors with necrosis (P = 0.003). A doubling of sB7-H1 levels was associated with a 41% increased risk of death (P = 0.010). Our observations suggest that sB7-H1 may be detected in the sera of ccRCC patients and that sB7-H1 may systemically impair host immunity, thereby fostering cancer progression and subsequent poor clinical outcome.
              Article 0 comments Cited 158 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Bingshan Liu: liubingshan@hotmail.com
                Yongping Song: songyongping001@163.com
                Delong Liu:
                ORCID: http://orcid.org/0000-0003-4502-4949
                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 December 2017
                Publication date PMC-release: 1 December 2017
                Publication date Collection: 2017
                Volume: 10
                Electronic Location Identifier: 174
                Affiliations
                [1 ]ISNI 0000 0004 1799 4638, GRID grid.414008.9, School of Basic Medical Sciences and the Affiliated Cancer Hospital of Zhengzhou University, ; Zhengzhou, China
                [2 ]ISNI 0000 0004 1799 4638, GRID grid.414008.9, Henan Cancer Hospital and the Affiliated Cancer Hospital of Zhengzhou University, ; 127 Dongming Road, Zhengzhou, 450008 China
                Author information
                http://orcid.org/0000-0003-4502-4949
                Article
                Publisher ID: 541
                DOI: 10.1186/s13045-017-0541-9
                PMC ID: 5712158
                PubMed ID: 29195503
                SO-VID: 89f3d791-df8c-4e7e-b45a-88d6f99f6bcd
                Copyright © © The Author(s). 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 : 17 October 2017
                Date accepted : 15 November 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: NSFC grant no. 81470287, YPS
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

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

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