{"id":"CU24095","slug":"kdm1a-inhibitor-combination--CU24095","source":{"id":"CU24095","dataset":"techtransfer","title":"KDM1A inhibitor combination therapy to enhance antibody-drug conjugate efficacy in carcinomas","description_":"<p>This technology is a KDM1A inhibitor that improves carcinoma sensitivity to FDA-approved antibody-drug conjugates by epigenetically reprogramming tumor cell to increase surface expression of antigens.</p>\r\r<h2>Unmet Need: Treatment to improve tumor response to antibody-drug conjugate therapies</h2>\r\r<p>Antibody-drug conjugates (ADCs) deliver cytotoxic payloads to tumor cells by recognizing specific cell surface antigens, enabling improved efficacy at the treatment site with fewer side effects. However, many tumors exhibit low or heterogeneous expression of these target antigens, limiting ADC effectiveness and leading to treatment resistance. While several ADCs have been approved for metastatic cancers, their benefit is often restricted to patients with sufficient antigen expression. There is a need for strategies that increase target antigen expression to improve ADC efficacy and expand treatment opportunities for patients with ADC-resistant tumors. </p>\r\r<h2>The Technology: KDM1A inhibitor to improve tumor targeting by antibody-drug conjugates</h2>\r\r<p>This technology is a KDM1A (lysine-specific demethylase 1A) inhibitor that epigenetically reprograms carcinoma cells to overexpress the ADC-targeted antigens NECTIN4 and/or TROP2 to increase their sensitivity to ADC therapies across bladder, breast, and other carcinomas. As such, a greater proportion of these tumors, even those expressing low levels of ADC-targeted antigens, can be altered to improve the targetability of ADCs, thereby increasing delivery of the chemotherapeutic drug to maximize cancer-killing potential.</p>\r\r<p>This technology has been validated in human patient-derived bladder cancer organoids. Treatment with KDM1A inhibitors (including GSK-LSD1 and ORY-1001) led to increased expression of NECTIN4 and TROP2. In combination with FDA-approved ADCs Enfortumab vedotin and Sacituzumab govitecan, this technology enhanced tumor sensitivity compared to ADC treatment alone.</p>\r\r<h2>Applications:</h2>\r\r<ul>\r<li>Combination therapy to enhance antibody-drug conjugate (ADC) efficacy in bladder cancer</li>\r<li>Combination therapy for metastatic triple-negative breast cancer</li>\r<li>Combination therapy with HER2-directed ADCs (e.g., Trastuzumab deruxtecan, Trastuzumab emtansine)</li>\r<li>Combination therapy with radiation therapy to further enhance ADC response</li>\r<li>Treatment of ADC-resistant and metastatic cancers</li>\r<li>Personalized therapy for tumor with low antigen expression</li>\r<li>Research tool for epigenetic reprogramming of cancer cells</li>\r<li>Research tool for inducing NECTIN4 and TROP2 expression</li>\r<li>Research tool for improving tumor targeting with ADCs and other biologics</li>\r<li>Platform to support development of next-generation ADC therapies</li>\r</ul>\r\r<h2>Advantages:</h2>\r\r<ul>\r<li>Improves response of bladder cancer to existing FDA-approved antibody-drug conjugate (ADC) therapies </li>\r<li>Expands therapeutic opportunities for ADC-resistant or antigen-low tumors</li>\r<li>Provides treatment options for tumors that develop resistance during treatment</li>\r<li>Enables higher effective chemotherapeutic dosing with fewer side effects</li>\r<li>Compatible with several existing ADC therapies</li>\r</ul>\r\r<h2>Lead Inventor:</h2>\r\r<p><a href=\"https://www.genetics.cuimc.columbia.edu/profile/michael-m-shen-phd\">Michael Shen, Ph.D.</a></p>\r\r<h2>Patent Information:</h2>\r\r<p>Patent Pending(<a href=\"https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2026076330&amp;_cid=P12-MNUVHT-13089-1\">WO/2026/076330</a>)</p>\r\r<h2>Related Publications:</h2>\r\r<ul>\r<li><a href=\"https://pubmed.ncbi.nlm.nih.gov/29625057/\">Lee SH, Hu W, Matulay JT, Silva MV, Owczarek TB, Kim K, Chua CW, Barlow LJ, Kandoth C, Williams AB, Bergren SK, Pietzak EJ, Anderson CB, Benson MC, Coleman JA, Taylor BS, Abate-Shen C, McKiernan JM, Al-Ahmadie H, Solit DB, Shen MM. “Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer” Cell. 2018 Apr 5; 173(2): 515-528.</a></li>\r</ul>\r\r<h2>Tech Ventures Reference:</h2>\r\r<ul>\r<li><p>IR CU24095</p></li>\r<li><p>Licensing Contact: <a href=\"mailto:techtransfer@columbia.edu\">Joan Martinez</a> </p></li>\r</ul>\r","tags":["Antibody-drug conjugate","Antigen","Biopharmaceutical","Bladder cancer","Breast cancer","Chemotherapy","Combination therapy","Epigenetics","Metastasis","Organoid","Radiation therapy","Reprogramming","Triple-negative breast cancer"],"file_number":"CU24095","collections":[],"meta_description":"KDM1A inhibitors epigenetically upregulate NECTIN4/TROP2, boosting ADC efficacy in carcinomas and overcoming antigen-low resistance.","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":3.0,\"scalability\":3.0,\"timeliness\":4.0},\"weighted_score\":3.85,\"risks\":[\"Novel mechanism combining KDM1A inhibition with ADCs is moderately novel but builds on existing ADCs and epigenetic strategies.\",\"Readiness relies on organoid data; need in vivo validation and safety for combination.\",\"Scalability may be limited by access to ADCs and potential toxicity.\",\"Timeliness is solid given FDA-approved ADCs but regulatory path for combination needs clarity.\"],\"one_sentence_take\":\"KDM1A inhibition to upregulate ADC targets offers a strong near-term translational path with meaningful impact, but requires further in vivo safety data and regulatory alignment for combination use.\"}","inventors":["John Robert Christin","Michael Shen Ph.D."],"manager":"Joan Martinez","depts":["Medicine"],"divs":["Columbia University Medical Center (CUMC)"],"date_released":"2024-07-09"},"highlight":{},"matched_queries":null,"score":0.0}