NIH Ni F, Tang H, Wang C, Zhang H, Zheng C, Zhang N, Chen B, Sun L. Cancer Manag Res. Tumor immunity CD40 Pancreatic cancer Macrophages T cells CIMT 2012 This paper is a Focussed Research Review based on a presentation given at the 10th annual meeting of the association for cancer immunotherapy … Tumor-associated myeloid cells: diversity and therapeutic targeting. Singh MP, Sethuraman SN, Miller C, Malayer J, Ranjan A. Theranostics. doi: 10.1002/14651858.CD011123.pub2. Pancreatic cancer: role of the immune system in cancer progression and vaccine-based immunotherapy. Side effects can … Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. J Immunother Cancer. COVID-19 is an emerging, rapidly evolving situation. Please enable it to take advantage of the complete set of features! Epub 2020 May 8. CSF-1R-Dependent Lethal Hepatotoxicity When Agonistic CD40 Antibody Is Given before but Not after Chemotherapy. CD40 activation as potential tool in malignant neoplasms. COVID-19 is an emerging, rapidly evolving situation. The vaccine is made up of inactivated pancreatic cancer cells, … May 7, 2018. 2021 Jan 1;11(2):540-554. doi: 10.7150/thno.49517. 2011 Mar 25;331(6024):1612-6. doi: 10.1126/science.1198443. AACR 2019: CD40 combination therapy can shrink pancreatic tumours 3 Apr 2019 A new combination of immunotherapy and chemotherapy for pancreatic cancer caused tumours to shrink in … Conflict of interest The authors declare that they have no conflicts of interest to disclose.  |  John Schieszer. Updated risk factors to inform early pancreatic cancer screening and identify high risk patients. Epub 2020 Mar 12. Mantovani A, Marchesi F, Jaillon S, Garlanda C, Allavena P. Cell Mol Immunol. Findings suggest that CD40 agonists can mediate both T-cell-dependent and T-cell-independent immune mechanisms of tumor regression in mice and patients. By blocking PD-1, this drug boosts the immune response against pancreatic cancer cells and can often shrink tumors. 2020 Nov 10;11:605619. doi: 10.3389/fimmu.2020.605619. Mol Carcinog. Please enable it to take advantage of the complete set of features! J Hematol Oncol. Here, we describe both laboratory and clinical efforts to target the CD40 pathway for immunotherapy in PDA. R01 CA229803/CA/NCI NIH HHS/United States, P01 CA210944/CA/NCI NIH HHS/United States, P30 CA016520/CA/NCI NIH HHS/United States, NCI CPTC Antibody Characterization Program. eCollection 2019. While most vaccines are administered to prevent disease, this vaccine is used on patients already diagnosed with pancreatic cancer.  |  Dendritic cell vaccination and CD40-agonist combination therapy licenses T cell-dependent antitumor immunity in a pancreatic carcinoma murine model. CD40 immunotherapy for pancreatic cancer Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive and lethal cancer which is poorly responsive to standard therapies. T-cell-independent mechanisms are associated with macrophage activation and the destruction of PDA tumor stroma, supporting the concept that immune modulation of the tumor microenvironment represents a useful approach in cancer immunotherapy. Evidence to date suggests that CD40 activation is a critical and nonredundant mechanism to convert so-called cold tumors to hot ones (with prominent tumor infiltration of T cells), sensitizing them to checkpoint inhibition. Although the PDA … Despite the fact that it only accounts for about three percent of new cancer cases, it is responsible for more than seven percent of all cancer … Would you like email updates of new search results? Pancreas cancer is classically a cold tumor and immunotherapy has had minimal efficacy for the treatment of this disease, unlike many others. 2021 Jan 6;23(1):5. doi: 10.1186/s13075-020-02372-z. 2020 Aug 10;485:56-65. doi: 10.1016/j.canlet.2020.04.022. However, it’s the subject of a lot of research. Our thinking is to combine a checkpoint inhibitor with an anti-CD40 therapy in pancreatic cancer, lung cancer or other nonresponding tumors. CD40; cancer; immunotherapy; pancreatic cancer. This site needs JavaScript to work properly. Front Immunol. The idea is that you need to stimulate the immune system to drive into the cancer … In a recent study sponsored by the Parker Institute of Cancer Immunotherapy of gemcitabine and nab-paclitaxel chemotherapy plus CD40 mAb APX005M, with or without PD-1 … Boiling histotripsy and in-situ CD40 stimulation improve the checkpoint blockade therapy of poorly immunogenic tumors. The former mechanism involves systemic activation of macrophages that infiltrate the tumor, become tumoricidal, and facilitate the depletion of tumor stroma. eCollection 2021. Although the results are early, we see encouraging signs that anti-CD40 immunotherapy, checkpoint inhibition, and chemotherapy in combination could be an effective new approach to treat … Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive and lethal cancer which is poorly responsive to standard therapies. CD40 agonists can mediate both T-cell-independent and T-cell-dependent immune mechanisms of tumor regression…, NLM eCollection 2020. 2017 Oct 1;23(19):5846-5857. doi: 10.1158/1078-0432.CCR-17-0285. 271 Background: Pancreatic cancer is well known for its aggressive clinical course and resistance to chemotherapy.  |  HHS The Current Landscape of Antibody-based Therapies in Solid Malignancies. Eriksson E, Milenova I, Wenthe J, Ståhle M, Leja-Jarblad J, Ullenhag G, Dimberg A, Moreno R, Alemany R, Loskog A. Clin Cancer Res. doi: 10.1136/jitc-2020-000772. Cancer Lett. CD40 is expressed broadly in hematopoietic and nonhematopoietic tissues and regulates immunity (1) thus providing a tractable target pathway for cancer immunotherapy. Theranostics. 2020 Jul;59(7):775-782. doi: 10.1002/mc.23179. In clinical trials, they are usually given with other treatments, such as chemotherapy. We investigated the effectiveness of gemcitabine, albumin-bound paclitaxel and CD40 … CD40 agonists can mediate both T-cell-independent and T-cell-dependent immune mechanisms of tumor regression in pancreatic cancer. CD40/CD40L relevance for cancer immunotherapy The extraordinary ability of CD40/CD40L signaling to syn-chronize the innate, cellular and humoral branches of the immune response has inspired basic and clinical research for decades. Despite the fact that it only accounts for about three percent of new cancer cases , it is responsible for more than seven percent of all cancer … This site needs JavaScript to work properly. Epub 2016 Jun 9. This drug is given as an intravenous (IV) infusion every 2 or 3 weeks. Systemic treatments for metastatic cutaneous melanoma. Mechanistically, the combination of chemotherapy followed by CD40 mAb functions as an in situ vaccine; in addition, destruction of stroma by CD40-activated macrophages may enhance chemotherapy … Tumor-Derived Myeloid Cell Chemoattractants and T Cell Exclusion in Pancreatic Cancer. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it kills more Americans each year than any cancer type other than lung and colorectal. Clipboard, Search History, and several other advanced features are temporarily unavailable. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O'Dwyer PJ, Vonderheide RH. 2019 Dec 19;11:10609-10621. doi: 10.2147/CMAR.S228926. Given the general expression profile and biological activities of CD40… K08 CA138907/CA/NCI NIH HHS/United States, R01 CA158186/CA/NCI NIH HHS/United States, R01 CA169123/CA/NCI NIH HHS/United States, P30 CA016520/CA/NCI NIH HHS/United States, T32 HL007775/HL/NHLBI NIH HHS/United States, NCI CPTC Antibody Characterization Program. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error, CD40 agonists can mediate both T-cell-independent and T-cell-dependent immune mechanisms of tumor regression in pancreatic cancer. Pasquali S, Hadjinicolaou AV, Chiarion Sileni V, Rossi CR, Mocellin S. Cochrane Database Syst Rev. A Phase I trial of CD40 immunotherapy in combination with gemcitabine demonstrated the combination was safe and achieves tumor responses in patients with pancreatic ductal adenocarcinoma. CD40 is an upstream mechanism of activation.  |  Hum Vaccin Immunother. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. 2020 Jul;108(1):363-376. doi: 10.1002/JLB.3MIR0320-475R. Read on to learn … Cancer Immunol Immunother. 2019 Jul 12;12(1):76. doi: 10.1186/s13045-019-0760-3. Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus. Attention has largely focused on … Would you like email updates of new search results? Anti-CD40 antibody KPL-404 inhibits T cell-mediated activation of B cells from healthy donors and autoimmune patients. Epub 2018 Jan 13. To date, the U.S. Food and Drug Administration (FDA) has not approved an immunotherapy for pancreatic cancer. The interplay between innate and adaptive immunity in cancer shapes the productivity of cancer immunosurveillance. Epub 2016 May 23. SEA-CD40 is an agent, which is going to try and stimulate the immune system. One is an experimental antibody that targets the CD40 protein and propels the immune … 2014;10(11):3354-68. doi: 10.4161/hv.34392. J Immunol. 2020 Jul;8(2):e000772. Understanding the immune landscape and tumor microenvironment of pancreatic cancer to improve immunotherapy. Robert H Vonderheide Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, …  |  Baohuoside I Inhibits the Proliferation of Pancreatic Cancer Cells via mTOR/S6K1-Caspases/Bcl2/Bax Apoptotic Signaling. 2016 Jul 1;197(1):179-87. doi: 10.4049/jimmunol.1600146. The former mechanism involves systemic activation of … In combination with chemotherapy, CD40 agonists can also activate T-cell immunity and mediate major tumor regression; however, anti-tumor T-cell responses can be inhibited by suppressive elements in the tumor microenvironment. CD40 immunotherapy for pancreatic cancer. Although the PDA tumor microenvironment is considered especially immunosuppressive, recent data mostly from genetically engineered and other mouse models of the disease suggest that novel immunotherapeutic approaches hold promise. Epub 2016 May 23. Antitumor activity with or without anti-CTLA4 monoclonal antibody (mAb) therapy has been observed in patients with melanoma, and major tumor regressions have been observed in patients with pancreatic cancer, mesothelioma, and other tumors in combination with chemotherapy. In addition to standard-of-care chemotherapy, we attack the tumor with two different immunotherapy agents. Natural killer cells have become an increasingly important target for cancer immunotherapy since they have demonstrated to mediate successful and efficient anti‐tumor responses. eCollection 2021. 39, 40 They play an … Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it kills more Americans each year than any cancer type other than lung and colorectal. Clipboard, Search History, and several other advanced features are temporarily unavailable. Byrne KT, Leisenring NH, Bajor DL, Vonderheide RH. John Schieszer. Mechanistically, the combination of chemotherapy followed by CD40 mAb functions as an in situ vaccine; in addition, destruction of stroma by CD40-activated macrophages may enhance chemotherapy delivery. See this image and copyright information in PMC. HHS Shah A, Rauth S, Aithal A, Kaur S, Ganguly K, Orzechowski C, Varshney GC, Jain M, Batra SK. USA.gov. Epub 2020 Apr 9. 2021 Jan 20. doi: 10.1038/s41423-020-00613-4. Activating CD40 is “a key to initiating a T-cell response to tumors,” says Dr. Robert Vonderheide, MD, director of U Penn’s Abramson Cancer Center. CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in Cancer. 2018 Apr;67(4):639-652. doi: 10.1007/s00262-018-2115-2. Ottaiano A, Pisano C, De Chiara A, Ascierto PA, Botti G, Barletta E, Apice G, Gridelli C, Iaffaioli VR. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Robert Vonderheide, M.D., D.Phil., a member of CRI’s Scientific Advisory Council, is leading a CRI clinical trial that is targeting the CD40 pathway in combination with chemotherapy and checkpoint … Epub 2017 May 23. CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily.  |  2021 Jan 1;11(3):1493-1512. doi: 10.7150/thno.52614. 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