For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
32
views
30
references
 Top references
cited by
0
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      652
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      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

          This study evaluated the effects of combining an OX40 agonistic antibody (aOX40) with a cell vaccine targeting HER2/neu, called “Triplex”. Such HER2/neu cell vaccine included two biological adjuvants (interleukin 12 (IL12) and allogeneic histocompatibility antigens) and was previously found able to prevent autochthonous HER2/neu-driven mammary carcinogenesis. Timing of aOX40 administration, concomitantly or after cell vaccination, gave opposite results. Unexpectedly, vaccine efficacy was hampered by concomitant OX40 triggering. Such decreased immunoprevention was likely due to a reduced induction of anti-HER2/neu antibodies and to a higher level of Treg activation. On the contrary, aOX40 administration after the completion of vaccination slightly but significantly increased immunopreventive vaccine efficacy, and led to increased production of GM-CSF and IL10. In conclusion, OX40 triggering can either impair or ameliorate immunoprevention of HER2/neu-driven mammary carcinogenesis depending on the schedule of aOX40 administration.

          Related collections

          Most cited references30

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

          Eradication of spontaneous malignancy by local immunotherapy

          Idit Sagiv-Barfi, Ronald Levy, Sanjiv Gambhir … (2018)
          It has recently become apparent that the immune system can cure cancer. In some of these strategies, the antigen targets are preidentified and therapies are custom-made against these targets. In others, antibodies are used to remove the brakes of the immune system, allowing preexisting T cells to attack cancer cells. We have used another noncustomized approach called in situ vaccination. Immunoenhancing agents are injected locally into one site of tumor, thereby triggering a T cell immune response locally that then attacks cancer throughout the body. We have used a screening strategy in which the same syngeneic tumor is implanted at two separate sites in the body. One tumor is then injected with the test agents, and the resulting immune response is detected by the regression of the distant, untreated tumor. Using this assay, the combination of unmethylated CG–enriched oligodeoxynucleotide (CpG)—a Toll-like receptor 9 (TLR9) ligand—and anti-OX40 antibody provided the most impressive results. TLRs are components of the innate immune system that recognize molecular patterns on pathogens. Low doses of CpG injected into a tumor induce the expression of OX40 on CD4+ T cells in the microenvironment in mouse or human tumors. An agonistic anti-OX40 antibody can then trigger a T cell immune response, which is specific to the antigens of the injected tumor. Remarkably, this combination of a TLR ligand and an anti-OX40 antibody can cure multiple types of cancer and prevent spontaneous genetically driven cancers.
          Article 0 comments Cited 135 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

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

            Walter Urba, Zipei Feng, David J Friedman … (2017)
            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.
            Article 0 comments Cited 135 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Rationale for anti-OX40 cancer immunotherapy.

              Sandrine Aspeslagh, Sophie Postel-Vinay, Sylvie Rusakiewicz … (2016)
              Immune checkpoint blockade with antagonistic monoclonal antibodies (mAbs) targeting B7 immunoglobulin superfamily molecules (CTLA-4, PD-1, and PD-L1) generate long lasting anti-tumour immune responses translating into clinical benefit across many cancer types. However, many patients are primarily resistant to immune checkpoint blockade -based monotherapy and many others will eventually relapse. Therefore, new immunostimulatory targets are needed to overcome primary and secondary resistance to immunotherapy. Besides the B7 co-inhibitory receptors, the tumour necrosis factor receptor superfamily contains many other immune checkpoints, which could become the next generation immunomodulators. Among them stands OX40 (CD134), a co-stimulatory molecule that can be expressed by activated immune cells. Several anti-OX40 agonistic monoclonal antibodies are currently tested in early phase cancer clinical trials. Accumulating preclinical evidence supports their clinical development. However, conflicting results and controversies between in vitro and in vivo data point to the need for comprehensive ancillary studies to be performed in upcoming clinical trials to better understand the mechanism of action of anti-OX40 mAbs-based therapy.
              Article 0 comments Cited 125 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Oncoimmunology
                Journal ID (iso-abbrev): Oncoimmunology
                Journal ID (publisher-id): KONI
                Journal ID (publisher-id): koni20
                Title: Oncoimmunology
                Publisher: Taylor & Francis
                ISSN (Print): 2162-4011
                ISSN (Electronic): 2162-402X
                Publication date Collection: 2018
                Publication date (Electronic): 11 June 2018
                Publication date PMC-release: 11 June 2018
                Volume: 7
                Issue: 8
                Electronic Location Identifier: e1465164
                Affiliations
                [a ]Laboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna , Italy
                [b ]Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milano, Italy
                [c ]Rizzoli Orthopedic
                ScienceOpen disciplines: Immunology
                Keywords: cancer vaccine,her2/neu,immunoprevention,mammary cancer,ox40
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: cancer vaccine, her2/neu, immunoprevention, mammary cancer, ox40

                Comments

                Comment on this article