{"id":"CU17258","slug":"synergistic-epigenetic--CU17258","source":{"id":"CU17258","dataset":"techtransfer","title":"Synergistic epigenetic combination therapy to treat germinal center derived lymphomas","description_":"<p>This technology is a method for treating germinal center (GC) diffuse large B-cell lymphoma (DLBCL) and other lymphomas using an epigenetic combination therapy targeting EZH2 dysregulation and HDAC-mediated epigenetic repression.</p>\r\r<h2>Unmet Need: Combination treatment for relapsed/refractory GC-DLBCL</h2>\r\r<p>Germinal center (GC) diffuse large B-cell lymphoma (DLBCL) is strongly linked to mutations in epigenetic modulators, such as histone methyltransferases (e.g. EZH2, MLL) and histone acetyltransferases (e.g. EP300, CREBBP). EZH2 activating mutations and loss of histone acetyltransferase function can switch off genes that normally keep abnormal cell growth in check, allowing lymphoma cells to survive and grow more aggressively. Approximately 30% of DLBCL patients relapse following first-line treatment, requiring second-line chemotherapy followed by autologous stem cell transplantation (AutoSCT). However, some patients are not eligible for AutoSCT or relapse afterward, highlighting the need for alternative targeted therapies. Furthermore, there are currently no treatments for GC-DLBCL utilizing a drug combination targeting EZH2 and HDACs.</p>\r\r<h2>The Technology: Synergistic epigenetic combination therapy for GC-DLBCL</h2>\r\r<p>This technology describes the use of a combination of drugs to target epigenetic modulators as a therapy for GC-DLBCL. This combination therapy elicits a synergistic effect by dual inhibition of EZH2 and HDAC. By inhibiting EZH2-mediated repression and HDAC-mediated chromatin tightening, this approach may restore gene expression for regulating lymphoma cell growth, differentiation, and survival. A BCL2 inhibitor may also be combined to further promote cancer cell death by blocking anti-apoptotic survival signaling. As a result, this treatment has the potential to offer improved outcomes for GC-DLBCL patients compared with other chemotherapeutic approaches, including higher overall response rates, longer response durations, and improved progression-free survival.</p>\r\r<p>This technology has been validated in a panel of lymphoma cell lines and in a xenograft mouse model of GC-DLBCL.</p>\r\r<h2>Applications:</h2>\r\r<ul>\r<li>Therapy for GC-DLBCL patients who have relapsed and are not eligible for AutoSCT</li>\r<li>Therapy for GC-DLBCL patients who have relapsed after AutoSCT</li>\r<li>Treatment for other lymphomas associated with defects in epigenetic modulators like EZH2 </li>\r<li>More specific and targeted therapy for EZH2-dysregulated lymphoma (e.g. GC-DLBCL or adult T-cell leukemia lymphoma (ATLL)) due to EZH2 gene mutation or overexpression</li>\r</ul>\r\r<h2>Advantages:</h2>\r\r<ul>\r<li>Provides a treatment method for currently untreatable relapsed and refractory GC-DLBCL</li>\r<li>Combination therapy uses drugs that are already available</li>\r<li>Synergistic effect of dual EZH2 and HDAC inhibition </li>\r<li>Potential synergistic combination of BCL2 inhibitor with EZH2 and HDAC inhibitors </li>\r<li>Potential administration of EZH2 and HDAC inhibitors simultaneously, sequentially, or separately</li>\r<li>Potential synergistic increase in cancer cell apoptosis or reduction of tumor volume using dual inhibitor therapy</li>\r<li>Potential administration as a small molecule, polynucleotide, or antibody or antigen-binding portion thereof</li>\r</ul>\r\r<h2>Lead Inventor:</h2>\r\r<p><a href=\"http://cancer.columbia.edu/jennifer-e-amengual-md\">Jennifer Amengual, M.D.</a></p>\r\r<h2>Patent Information:</h2>\r\r<p>Patent Issued (US <a href=\"https://patents.google.com/patent/US11597933B2/en\">11,597,933</a>)</p>\r\r<h2>Related Publications:</h2>\r\r<ul>\r<li><p><a href=\"https://ashpublications.org/blood/article/146/Supplement%201/1773/549105/Dual-HDAC-and-EZH2-inhibition-modulates-RFX5\">Piorczynski T, Pazos M, Tolu S, Tanna A, Amengual JE. “Dual HDAC and EZH2 inhibition modulates RFX5 activity to increase the immunogenicity of germinal center-derived B-cell lymphoma” Blood. 2025 Nov 3;146:1773</a></p></li>\r<li><p><a href=\"https://ashpublications.org/blood/article/138/Supplement%201/2410/478533/Dual-Targeting-of-EZH2-and-HDAC-with-Tazemetostat\">Ricker EC, Estrella B, Pazos II MA, Amengual JE. “Dual targeting of EZH2 and HDAC with tazemetostat and belinostat promotes immunogenicity in GC-DLBCL” Blood. 2021 Nov 23;138:2410.</a></p></li>\r<li><p><a href=\"https://pubmed.ncbi.nlm.nih.gov/30979734/\">Lue JK, Prabhu SA, Liu Y, Gonzalez Y, Verma A, Mundi PS, Abshiru N, Camarillo JM, Mehta S, Chen EI, Qiao C. “Precision targeting with EZH2 and HDAC inhibitors in epigenetically dysregulated lymphomas” Clinical Cancer Research. 2019 Sep 1;25(17):5271-83.</a></p></li>\r<li><p><a href=\"https://ashpublications.org/blood/article/128/22/839/99333/Epigenetic-Targeting-with-EZH2-and-HDAC-Inhibitors\">Lue JK, Prabhu SA, Liu Y, O’Connor OA, Amengual JE. “Epigenetic targeting with EZH2 and HDAC inhibitors is synergistic in EZH2 deregulated lymphomas” Blood. 2016 Dec 2;128(22):839.</a></p></li>\r<li><p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/24857928\">Amengual JE, O’Connor OA. “Manipulating the epigenome in germinal center lymphomas: is it getting easier and ezier?” Clinical Cancer Research. 2014 Jun 15; 20(12): 3047-3049.</a></p></li>\r<li><p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/26141799\">Lue JK, Amengual JE, O’Connor OA. “Epigenetics and Lymphoma: Can We Use Epigenetics to Prime or Reset Chemoresistant Lymphoma Programs?” Current Oncology reports. 2015 Sep; 17(9): 40.</a></p></li>\r</ul>\r\r<h2>Tech Ventures Reference:</h2>\r\r<ul>\r<li><p>IR CU17258</p></li>\r<li><p>Licensing Contact: <a href=\"mailto:techtransfer@columbia.edu\">Jerry Kokoshka</a></p></li>\r</ul>\r","tags":["Apoptosis","B-cell lymphoma","Bcl-2","CREB-binding protein","Chemotherapy","Chromatin","Combination therapy","Diffuse large B-cell lymphoma","Disease","Enzyme inhibitor","Epigenetics","Epigenome","Gene","Germinal center","Histone","Histone acetyltransferase","Histone deacetylase","Histone deacetylase inhibitor","Immunogenicity","Lymphoma","Monoclonal antibody","Mutation","Neoplasm","Progression-free survival","Small molecule","Targeted therapy","Xenotransplantation"],"file_number":"CU17258","collections":[{"key":427,"name":"Oncology"}],"meta_description":"Synergistic therapy combining EZH2 and HDAC inhibitors, possibly with BCL2 block, to treat relapsed GC-DLBCL epigenetically.","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":3.0,\"scalability\":3.0,\"timeliness\":2.0},\"weighted_score\":3.2,\"risks\":[\"Older than 3 years (2018) -> penalty applied to timeliness\",\"Translational readiness not yet proven in humans; reliance on existing drugs may lead to competitive/regulatory challenges\",\"Potential safety/toxicity concerns with combination epigenetic therapy\"],\"one_sentence_take\":\"Strong novelty with dual epigenetic targeting and clear clinical rationale, but timeliness is limited by age and translational readiness.\"}","inventors":["Jennifer Amengual","Jennifer Lue","Owen O'Connor"],"manager":"Jerry Kokoshka","depts":["Medicine","Oncology"],"divs":["Columbia University Medical Center (CUMC)"],"date_released":"2018-01-03"},"highlight":{},"matched_queries":null,"score":0.0}