12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Magnetic Resonance Colonography Enables the Efficacy Assessment of Immune Checkpoint Inhibitors in an Orthotopic Colorectal Cancer Mouse Model 1

      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

          Immune checkpoint inhibitors (ICIs) have become an effective therapeutic option for colorectal cancer and studies on these drugs have therefore increased greatly. Efficacy assessments of ICIs in preclinical orthotopic colorectal cancer using MRI have not been reported however due to the difficulties in conducting colorectal imaging. The purpose of this present study was to investigate the feasibility of using magnetic resonance colonography (MRC) to evaluate the efficacy of an ICI, an anti-PD-L1 antibody, in an orthotopic colorectal cancer mouse model. The mouse model was generated by the engraftment of colorectal cancer cells into the submucosal layer of the colon. Anti-cancer efficacy was assessed by tumor volume and metastatic tumor number analyses, and these values were significantly lower in the PD-L1 antibody-treated group compared to the controls. Histological analyses using H&E and Ki-67 immunohistochemical staining confirmed a highly efficacious tumor growth inhibition and enhanced infiltration by CD4+ and CD8+ lymphocytes in the PD-L1 antibody-treated group. We conclude that MRC has the potential to be used for ICI efficacy assessments against orthotopic colorectal cancer mouse model.

          Related collections

          Most cited references23

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

          Immune Checkpoint inhibitors: An introduction to the next-generation cancer immunotherapy.

          Activating the immune system to eliminate cancer cells and produce clinically relevant responses has been a long-standing goal of cancer research. Most promising therapeutic approaches to activating antitumor immunity include immune checkpoint inhibitors. Immune checkpoints are numerous inhibitory pathways hardwired in the immune system. They are critical for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues to minimize collateral tissue damage. Tumors regulate certain immune checkpoint pathways as a major mechanism of immune resistance. Because immune checkpoints are initiated by ligand-receptor interactions, blockade by antibodies provides a rational therapeutic approach. Although targeted therapies are clinically successful, they are often short-lived due to rapid development of resistance. Immunotherapies offer one notable advantage. Enhancing the cell-mediated immune response against tumor cells leads to generation of a long-term memory lymphocyte population patrolling the body to attack growth of any new tumor cells, thereby sustaining the therapeutic effects. Furthermore, early clinical results suggest that combination immunotherapies offer even more potent antitumor activity. This review is intended to provide an introduction to immune checkpoint inhibitors and discusses the scientific overview of cancer immunotherapy, mechanisms of the inhibitors, clinical pharmacology considerations, advances in combination therapies, and challenges in drug development.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The emerging role of immunotherapy in colorectal cancer.

            Modulation of the interaction between the immune system and the tumor microenvironment has long been a target of cancer research, including colorectal cancer (CRC). Approaches explored to date include vaccines (autologous, peptide, dendritic cell, viral and bacterial), cytokine therapy, toll-like receptors (TLRs), autologous cell therapy and checkpoint inhibition. Until recently these approaches have been shown to have only modest efficacy in reducing tumor burden. However, significant breakthroughs have been made, with the use of checkpoint inhibitors targeting programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4). Immunotherapy now represents a possible avenue of curative treatment for those with chemo-otherwise refractory tumors. Success with this approach to immunotherapy has largely been confined to tumors with high mutational burdens such as melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer. This observation led to the exploration and successful use of checkpoint inhibitors in those with mismatch repair colorectal cancer which have a relatively high mutational burden. Ongoing trials are focused on further exploring the use of checkpoint inhibitors in addition to investigating the various combinations of immunotherapeutic drugs.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Non-invasive molecular imaging for preclinical cancer therapeutic development.

              Molecular and non-invasive imaging are rapidly emerging fields in preclinical cancer drug discovery. This is driven by the need to develop more efficacious and safer treatments, the advent of molecular-targeted therapeutics, and the requirements to reduce and refine current preclinical in vivo models. Such bioimaging strategies include MRI, PET, single positron emission computed tomography, ultrasound, and optical approaches such as bioluminescence and fluorescence imaging. These molecular imaging modalities have several advantages over traditional screening methods, not least the ability to quantitatively monitor pharmacodynamic changes at the cellular and molecular level in living animals non-invasively in real time. This review aims to provide an overview of non-invasive molecular imaging techniques, highlighting the strengths, limitations and versatility of these approaches in preclinical cancer drug discovery and development. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.
                Bookmark

                Author and article information

                Contributors
                Journal
                Transl Oncol
                Transl Oncol
                Translational Oncology
                Neoplasia Press
                1936-5233
                11 July 2019
                September 2019
                11 July 2019
                : 12
                : 9
                : 1264-1270
                Affiliations
                [* ]Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
                []Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
                []Scripps Korea Antibody Institute, Chuncheon, Gangwon-do, Republic of Korea
                [§ ]Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
                []Medical Research Institute, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung-si, Gangwon-do, Republic of Korea
                Author notes
                [* ]Address all correspondence to: Kyung-Won Kim, M.D., Ph.D., Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. or Yoonseok Choi, Ph.D., Medical Research Institute, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung-si, Gangwon-do, Republic of Korea. medimash@ 123456gmail.com yschoi21rad@ 123456gnah.co.kr
                [2]

                These authors contributed equally to this work.

                Article
                S1936-5233(19)30196-2
                10.1016/j.tranon.2019.06.006
                6626083
                31302474
                15c61707-a6e0-482d-8d4e-445a14d48720
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 22 April 2019
                : 19 June 2019
                Categories
                Original article

                Comments

                Comment on this article