7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          PD-L1 immunohistochemistry correlates only moderately with patient survival and response to PD-(L)1 treatment. Heterogeneity of tumor PD-L1 expression might limit the predictive value of small biopsies. Here we show that tumor PD-L1 and PD-1 expression can be quantified non-invasively using PET-CT in patients with non-small-cell lung cancer. Whole body PD-(L)1 PET-CT reveals significant tumor tracer uptake heterogeneity both between patients, as well as within patients between different tumor lesions.

          Abstract

          Assessment of PD-1 and PD-L1 expression can be predictive of immunotherapy response in lung cancer. Here the authors assess the clinical toxicity, safety and quality of non-invasive imaging of PD-1 and PD-L1 expression in 13 patients with advanced lung cancer prior to treatment with immunotherapy and show it correlates with response.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: found
          • Article: not found

          Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small-Cell Lung Cancer.

          Early-phase trials with monoclonal antibodies targeting PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death 1 ligand 1) have demonstrated durable clinical responses in patients with non-small-cell lung cancer (NSCLC). However, current assays for the prognostic and/or predictive role of tumor PD-L1 expression are not standardized with respect to either quantity or distribution of expression.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Conjugation and radiolabeling of monoclonal antibodies with zirconium-89 for PET imaging using the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine.

            The positron emitter zirconium-89 ((89)Zr) has very attractive properties for positron emission tomography (PET) imaging of intact monoclonal antibodies (mAbs) using immuno-PET. This protocol describes the step-by-step procedure for the facile radiolabeling of mAbs or other proteins with (89)Zr using p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS). First, Df-Bz-NCS is coupled to the lysine-NH(2) groups of a mAb at pH 9.0 (pre-modification), followed by purification using gel filtration. Next, the pre-modified mAb is labeled at room temperature by the addition of [(89)Zr]Zr-oxalic acid solution followed by purification using gel filtration. The entire process of pre-modification, radiolabeling and purification steps will take about 2.5 h.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40

              Purpose Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to impact patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T cell costimulatory receptors such as OX40 remains a critical question. Experimental Design We utilized an anti-PD-1 refractory, orthotopically-transplanted MMTV-PyMT mammary cancer model to investigate the anti-tumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. Since PD-1 naturally aids in immune contraction after T cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 followed by anti-PD-1. Results The concurrent addition of anti-PD-1 significantly attenuated the therapeutic effect of anti-OX40 alone. Combination-treated mice had considerable increases in type 1 and type 2 serum cytokines and significantly augmented expression of inhibitory receptors or exhaustion markers CTLA-4 and TIM-3 on T cells. Combination treatment increased intratumoral CD4 + T cell proliferation at day 13, but at day 19 both CD4 + and CD8 + T cell proliferation was significantly reduced compared to untreated mice. In two tumor models, sequential combination of anti-OX40 followed by anti-PD-1 (but not the reverse order) resulted in significant increases in therapeutic efficacy. Against MMTV-PyMT tumors sequential combination was dependent on both CD4 + and CD8 + T cells and completely regressed tumors in ~30% of treated animals. Conclusions These results highlight the importance of timing for optimized therapeutic effect with combination immunotherapies and suggest the testing of sequencing in combination immunotherapy clinical trials.
                Bookmark

                Author and article information

                Contributors
                j.d.langen@nki.nl
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                7 November 2018
                7 November 2018
                2018
                : 9
                : 4664
                Affiliations
                [1 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Department of Pulmonary Diseases, Cancer Center Amsterdam, , Amsterdam UMC, Vrije Universiteit Amsterdam, ; De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
                [2 ]GRID grid.419971.3, Bristol-Myers Squibb Research and Development, ; Route 206 & Province Line Rd., Princeton, NJ 08543 USA
                [3 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, , Amsterdam UMC, Vrije Universiteit Amsterdam, ; De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
                [4 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Department of Pathology, Cancer Center Amsterdam, , Amsterdam UMC, Vrije Universiteit Amsterdam, ; De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
                [5 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Department of Medical Oncology, Cancer Center Amsterdam, , Amsterdam UMC, Vrije Universiteit Amsterdam, ; De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
                [6 ]GRID grid.430814.a, Department of Thoracic Oncology, , Netherlands Cancer Institute, ; Plesmanlaan 2, 1066 CX Amsterdam, The Netherlands
                Author information
                http://orcid.org/0000-0002-1250-7656
                http://orcid.org/0000-0003-1464-8978
                Article
                7131
                10.1038/s41467-018-07131-y
                6220188
                30405135
                b66c7c5f-51bc-4e98-aa94-c738b1dc3867
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 June 2018
                : 3 October 2018
                Categories
                Article
                Custom metadata
                © The Author(s) 2018

                Uncategorized
                Uncategorized

                Comments

                Comment on this article