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PubMed | BioNovion, Dana-Farber Cancer Institute, Harvard University and Peking Union Medical College
Type: Journal Article | Journal: Blood | Year: 2016

Here we show that overexpression or activation of B-cell maturation antigen (BCMA) by its ligand, a proliferation-inducing ligand (APRIL), promotes human multiple myeloma (MM) progression in vivo. BCMA downregulation strongly decreases viability and MM colony formation; conversely, BCMA overexpression augments MM cell growth and survival via induction of protein kinase B (AKT), MAPK, and nuclear factor (NF)-B signaling cascades. Importantly, BCMA promotes in vivo growth of xenografted MM cells harboring p53 mutation in mice. BCMA-overexpressing tumors exhibit significantly increased CD31/microvessel density and vascular endothelial growth factor compared with paired control tumors. These tumors also express increased transcripts crucial for osteoclast activation, adhesion, and angiogenesis/metastasis, as well as genes mediating immune inhibition including programmed death ligand 1, transforming growth factor , and interleukin 10. These target genes are consistently induced by paracrine APRIL binding to BCMA on MM cells, which is blocked by an antagonistic anti-APRIL monoclonal antibody hAPRIL01A (01A). 01A is cytotoxic against MM cells even in the presence of protective bone marrow (BM) myeloid cells including osteoclasts, macrophages, and plasmacytoid dendritic cells. 01A further decreases APRIL-induced adhesion and migration of MM cells via blockade of canonical and noncanonical NF-B pathways. Moreover, 01A prevents in vivo MM cell growth within implanted human bone chips in SCID mice. Finally, the effect of 01A on MM cell viability is enhanced by lenalidomide and bortezomib. Taken together, these data delineate new molecular mechanisms of in vivo MM growth and immunosuppression critically dependent on BCMA and APRIL in the BM microenvironment, further supporting targeting this prominent pathway in MM.


BERKELEY, Calif. and OSS, The Netherlands, Dec. 06, 2016 (GLOBE NEWSWIRE) -- Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, announced today that Hans van Eenennaam, Ph.D., chief operational officer and executive director of Aduro Biotech Europe, and John Dulos, Ph.D., principal scientist, will be honored tonight by the Intellectual Property Owners Education Foundation (IPOEF) as winners of the 43rd Inventor of the Year Award for their work relating to the discovery of KEYTRUDA® (pembrolizumab). KEYTRUDA is marketed by Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the U.S. and Canada) and is the first FDA-approved PD-1 inhibitor for the treatment of select cancers. “It is an honor to have been part of the team whose work led to the discovery of KEYTRUDA and positively impacted the lives of many cancer patients,” said Dr. van Eenennaam. “Now as part of Aduro Biotech Europe, where we are focused on developing novel B-select antibodies to modulate the immune system, we are pleased to be collaborating once again with the MSD team on what we believe to be the best-in-class anti-CD27 therapeutic antibody.” Dr. Dulos, principal scientist and project team lead for Aduro’s anti-APRIL BION-1301 program, commented, “As a scientist, it is incredibly satisfying to have been part of a team whose discoveries today are having a meaningful impact on the lives of many patients with several cancer types.  We thank the Intellectual Property Owners Education Foundation for this honor and will continue to leverage our knowledge and discoveries in the field of immuno-oncology with the aim of helping cancer patients in need.” Hans van Eenennaam, Ph.D., a chemist by training, has nearly 15 years of experience in the pharmaceutical and biotechnology industry and in-depth expertise in the field of immunology.  He currently serves as chief operational officer and executive director of Aduro Biotech Europe, where he leads the development of new anti-cancer antibodies using the company’s proprietary B-select antibody technology.  Prior to its acquisition by Aduro in 2015, Dr. van Eenennaam served as chief operational officer of BioNovion, a company he co-founded in 2011 to focus on the development of innovative therapeutic antibodies in the field of immuno-oncology.  He is named as inventor on seven pending and granted patent families, including the patents for KEYTRUDA, and an author on over 25 publications.  Dr. van Eenennaam received his doctorate in autoimmune biochemistry (cum laude) from Radboud University Nijmegen, the Netherlands. John Dulos, Ph.D., an immunologist with more than 20 years of experience in the pharmaceutical and biotechnology industry, is a leader in the field of immunology, oncology and infectious diseases. He currently serves as principal scientist at Aduro Biotech Europe where he oversees research and development of the company’s proprietary anti-APRIL (A PRoliferation-Inducing Ligand)-targeting monoclonal antibody, BION-1301, for the treatment of multiple myeloma. Throughout his career at multiple companies, Dr. Dulos has applied his expertise in in vitro and in vivo pharmacology of small molecules, vaccines and antibodies from preclinical development through Phase 2 clinical studies.  He is named as an inventor on two patent applications relating to KEYTRUDA and an author on 16 peer-reviewed publications, including lead authorship on a 2012 paper that first described the immune stimulating activity of KEYTRUDA (Journal of Immunotherapy 35:169-78). Dr. Dulos received his doctorate from Utrecht University in the Netherlands. About the IPOEF Inventor of the Year Award Each year, the IPOEF recognizes outstanding recent inventions with its annual Inventor of the Year Award.  In 2016, the foundation is celebrating innovation that has led to breakthroughs in cancer treatment by honoring the inventors of six drugs in the field of immunotherapy oncology treatment, including Merck & Co.’s KEYTRUDA®.  To learn more about the IPOEF and this award, visit www.ipoef.org. About the Aduro - MSD Collaboration BioNovion B.V. and MSD, through a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, entered into a worldwide license agreement in 2014 for the development and commercialization of CD27 antibody agonists, and BioNovion received an up-front payment of $15 million. In 2015, BioNovion was acquired by Aduro Biotech and became its subsidiary, Aduro Biotech Europe B.V. Under the agreement, a Joint Research Committee was formed to advance the program. Aduro has been reimbursed for certain research activities and is eligible to receive future development, commercial and net sales milestone payments. In addition, Aduro is eligible to receive royalties in the mid-single digits to low teens based on any net sales of the product, if it is approved for marketing. About Aduro Aduro Biotech, Inc. is an immunotherapy company focused on the discovery, development and commercialization of therapies that transform the treatment of challenging diseases. Aduro's technology platforms, which are designed to harness the body's natural immune system, are being investigated in cancer indications and have the potential to expand into autoimmune and infectious diseases. Aduro's LADD technology platform is based on proprietary attenuated strains of Listeria that have been engineered to express tumor-associated antigens to induce specific and targeted immune responses. This platform is being developed as a treatment for multiple indications, including pancreatic, ovarian, lung and prostate cancers, mesothelioma and glioblastoma. Additionally, a personalized form of LADD, or pLADD, is being developed utilizing tumor neoantigens that are specific to an individual patient’s tumor. Aduro's STING Pathway Activator platform is designed to activate the intracellular STING receptor, resulting in a potent tumor-specific immune response. ADU-S100 is the first STING Pathway Activator compound to enter the clinic and is currently being evaluated in a Phase 1 study in patients with cutaneously accessible metastatic solid tumors or lymphomas. Aduro’s B-select monoclonal antibody platform includes a number of immune modulating assets in research and preclinical development. Aduro is collaborating with leading global pharmaceutical companies to expand its products and technology platforms. For more information, please visit www.aduro.com. This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding our intentions or current expectations concerning, among other things, the potential for our technology platforms, plans, and the potential for eventual regulatory approval of our product candidates. In some cases, you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” or the negative or plural of these words or similar expressions.  Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our history of net operating losses and uncertainty regarding our ability to achieve profitability, our ability to develop and commercialize our product candidates, our ability to use and expand our technology platforms to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our inability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, our reliance on third parties, and our ability to obtain and adequately protect intellectual property rights for our product candidates.  We discuss many of these risks in greater detail under the heading “Risk Factors” contained in our quarterly report on Form 10-Q for the quarter ended September 30, 2016, which is on file with the Securities and Exchange Commission. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.


Kenny E.F.,Trinity College Dublin | Quinn S.R.,Trinity College Dublin | Doyle S.L.,Trinity College Dublin | Vink P.M.,Janssen Infectious Diseases BVBA | And 2 more authors.
PLoS ONE | Year: 2013

B cells signal through both the B cell receptor (BCR) which binds antigens and Toll-like receptors (TLRs) including TLR9 which recognises CpG DNA. Activation of TLR9 synergises with BCR signalling when the BCR and TLR9 co-localise within an auto-phagosome-like compartment. Here we report that Bruton's tyrosine kinase (BTK) is required for synergistic IL6 production and up-regulation of surface expression of MHC-class-II, CD69 and CD86 in primary murine and human B cells. We show that BTK is essential for co-localisation of the BCR and TLR9 within a potential auto-phagosome-like compartment in the Namalwa human B cell line. Downstream of BTK we find that calcium acting via calmodulin is required for this process. These data provide new insights into the role of BTK, an important target for autoimmune diseases, in B cell activation. © 2013 Kenny et al.


Expected Filing of Investigational New Drug (IND) Application in 2017 Company to Host Conference Call Today to Provide Program Update, Including STELLAR,  at 5:30 a.m. PT/ 8:30 a.m. ET BERKELEY, Calif. and OSS, The Netherlands, Dec. 05, 2016 (GLOBE NEWSWIRE) -- Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, announced today that an anti-CD27 antibody developed by Aduro Biotech Europe and derived from its proprietary B-select technology has been selected to be advanced into clinical development by Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the U.S. and Canada), through a subsidiary.  CD27 has been recognized as having a critical role in activating a productive anti-cancer immune response and has demonstrated the potential to be combined with checkpoint inhibitors in pre-clinical studies. “Pre-clinical studies have shown that an anti-CD27 agonist can induce a T cell-mediated anti-cancer immune response, and in combination with PD-1 immune checkpoint inhibitors complete tumor eradication can be achieved,” said Hans van Eenennaam, Ph.D., chief operational officer, Aduro Biotech Europe. The CD27 antibody was licensed by MSD to advance as a part of their successful immunotherapy development program and was identified in close collaboration with Prof. Jannie Borst, Ph.D., professor at the University of Amsterdam and division head at the Netherlands Cancer Institute, through Aduro’s B-select monoclonal antibody technology. This technology includes a proprietary ultra-selective functional screening process to identify antibodies with unique binding properties against a broad repertoire of targets that can modulate the innate and adaptive arms of the immune system. “In 2014, prior to the acquisition by Aduro Biotech, BioNovion entered into a worldwide license agreement with MSD that covers the product candidate’s development and advancement through commercialization,” said Andrea van Elsas, Ph.D., chief scientific officer of Aduro Biotech Europe. “Both companies recognized the significant potential of targeting CD27 as a new and distinct mechanism in cancer immunotherapy, especially in the context of PD-1 checkpoint inhibitors, and were strongly committed to accelerate a quality candidate into the clinic.” Conference Call with Management Aduro’s management will host a conference call to review this announcement and provide a program update, including STELLAR, today at 5:30 a.m. PT/ 8:30 a.m. ET.  To participate in the conference call, please dial (844) 309-0604 (domestic) or (574) 990-9932 (international) and refer to conference ID 31336163. Live audio of the conference call will be simultaneously webcast and will be available to members of the news media, investors and the general public at http://investors.aduro.com/. About the Aduro - MSD Collaboration BioNovion B.V. and MSD, through a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, entered into a worldwide license agreement in 2014 for the development and commercialization of CD27 antibody agonists, and BioNovion received an up-front payment of $15 million. In 2015, BioNovion was acquired by Aduro Biotech and became its subsidiary, Aduro Biotech Europe B.V. Under the agreement, a Joint Research Committee was formed to advance the program. Aduro has been reimbursed for certain research activities and is eligible to receive future development, commercial and net sales milestone payments. In addition, Aduro is eligible to receive royalties in the mid-single digits to low teens based on any net sales of the product, if it is approved for marketing. About Aduro Aduro Biotech, Inc. is an immunotherapy company focused on the discovery, development and commercialization of therapies that transform the treatment of challenging diseases. Aduro's technology platforms, which are designed to harness the body's natural immune system, are being investigated in cancer indications and have the potential to expand into autoimmune and infectious diseases. Aduro's LADD technology platform is based on proprietary attenuated strains of Listeria that have been engineered to express tumor-associated antigens to induce specific and targeted immune responses. This platform is being developed as a treatment for multiple indications, including pancreatic, ovarian, lung and prostate cancers, mesothelioma and glioblastoma. Additionally, a personalized form of LADD, or pLADD, is being developed utilizing tumor neoantigens that are specific to an individual patient’s tumor. Aduro's STING Pathway Activator platform is designed to activate the intracellular STING receptor, resulting in a potent tumor-specific immune response. ADU-S100 is the first STING Pathway Activator compound to enter the clinic and is currently being evaluated in a Phase 1 study in patients with cutaneously accessible metastatic solid tumors or lymphomas. Aduro’s B-select monoclonal antibody platform includes a number of immune modulating assets in research and preclinical development. Aduro is collaborating with leading global pharmaceutical companies to expand its products and technology platforms. For more information, please visit www.aduro.com. This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding our intentions or current expectations concerning, among other things, the potential for the anti-CD27 antibody described above, our technology platforms, plans, and the potential for eventual regulatory approval of our product candidates. In some cases, you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” or the negative or plural of these words or similar expressions.  Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our history of net operating losses and uncertainty regarding our ability to achieve profitability, our ability to develop and commercialize our product candidates, our ability to use and expand our technology platforms to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our inability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, our reliance on third parties, and our ability to obtain and adequately protect intellectual property rights for our product candidates.  We discuss many of these risks in greater detail under the heading “Risk Factors” contained in our quarterly report on Form 10-Q for the quarter ended September 30, 2016, which is on file with the Securities and Exchange Commission. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

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