longfellow95 Friday, 07/06/18 12:02:31 PM Re: None Post # 181412 of 246830 Well, it's gratifying to know that in addition to the extremely well qualified Scientific Advisory Board, there is also an extremely well qualified Steering Committee for the trial, and they are all amongst the list of co-authors.
I had not heard them named previously until LP named them at the ASCO meeting.
Steering Committee:-
Dr. Steven Bremm. Chief, Neurosurgical Oncology, Co-Director, Penn Brain Tumor Center, Professor of Neurosurgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
Dr. Fabio Iwamoto. Dr. Iwamoto is a neuro-oncologist whose previous training includes a neurology residency at NewYork-Presbyterian/Weill Cornell Medical Center and a neuro-oncology fellowship at Memorial Sloan-Kettering Cancer Center. For over three years, Dr. Iwamoto was an attending physician and an investigator at the Neuro-oncology Branch, a trans-institute branch of the National Cancer Institute and National Institute of Neurological Disorders and Stroke, in Bethesda, MD. At the intramural NIH, Dr. Iwamoto was a principal investigator in early phase clinical trials for brain tumors and worked with laboratory and computational scientists on several translational projects in brain tumors.
Dr. Iwamoto was recruited to Columbia University as the Deputy Director of the Neuro-oncology Division and is actively developing the clinical and translational research components of this program. He is an expert in the diagnosis, management, and treatment of brain and spinal cord tumors as well as neurological complications of cancer.
Dr. Martin (“Mac”) Cheever is the Director and Principal Investigator of the Cancer Immunotherapy Trials Network (CITN) funded by the National Cancer Institute (NCI). The CITN is a network of immunotherapy investigators who are well established and recognized academic leaders in the field of immunology at 32 leading research institutions across the U.S. Dr. Cheever also spearheaded the multi-year project to evaluate and prioritize the 20 most important investigational agents for immunotherapy and the 75 most promising cancer vaccine targets. Dr. Cheever previously served as the Director of Solid Tumor Research at the Fred Hutchinson Cancer Research Center, and continues to be a Full Member (Professor) there.
Dr. Cheever’s research is focused on cancer immunotherapy, including T cell therapy and the development of cancer vaccines, especially for breast cancer. He co-founded an early biotech company developing cancer vaccines, and served as Vice President of Clinical Research and Medical Affairs for 8 years. In that capacity, he gained extensive experience with design and execution of cancer vaccine clinical trials, FDA related product approval issues and collaboration with major pharmaceutical companies.
Dr. Alfredo Quinones-Hinojosa.
Dr. Alfredo Quiñones-Hinojosa is currently Director of the Brain Tumor Surgery Program at Johns Hopkins Hospital. He is also head of the Brain Tumor Stem Cell Laboratory at Johns Hopkins. In September 2016, Dr. Quiñones will become the “William J. and Charles H. Mayo Professor” and Chair of Neurologic Surgery at the Mayo Clinic in Jacksonville, Florida, in connection with $100 million in major new construction projects being undertaken there, to develop new facilities and integrated services for complex cancers and for neurologic and neurosurgical care.
Dr. Quiñones has published 295 peer-reviewed papers and over 100 book chapters (including invited reviews and letters), and has been the main editor or section editor of nine textbooks. Most notably, Dr. Quiñones is also Editor-in-Chief for one of the most well-respected and widely-read neurosurgical textbooks in the world. Dr. Quiñones is one of the few brain surgeons with multiple research grants from the National Institutes of Health, as well as the Robert Wood Johnson Foundation and the Maryland Stem Cell Foundation. Some of his major accomplishments to date include: 1) elucidating mechanisms by which brain tumors migrate and metastasize, 2) integrating the use of stem cells into local treatment of solid tumors, 3) the concomitant use of nanotechnology and focal beam radiotherapy in the systemic treatment of solid tumors, 4) the development of new imaging software to help identify areas within solid tumors with the greatest malignant potential, and 5) the development of innovative, minimally invasive approaches to brain tumor resection. Dr. Quiñones is the Principal Investigator (PI) or Co-PI on multiple clinical trials, including novel combination therapies for brain tumors (with checkpoint inhibitors and/or various other technologies), and the first trials in the U.S. of certain technologies for more complete surgical removal of brain tumors.
Dr. Quinones has been recognized with the Association of American Medical Colleges Herbert W. Nickens Award, the Johns Hopkins Hospital Department of Neurosurgery, Richard J. Otenasek, Jr, Faculty Teaching Award, the “Neurosurgeon of the Year” award from Voices Against Brain Cancer, a “Health Care Heroes Award,” a Howard Hughes Medical Institute Physician-Scientist Early Career Award and various other recognitions.
Dr. Jerome Galon.
Dr. Galon is the Director of the Integrative Cancer Immunology Lab at INSERM (the French national institutes of health). He is associate Director and co-founder of European Academy of Tumor Immunology (EATI) and board Director of the Society for Immunotherapy of Cancer (SITC). He defined the concept of cancer immune-contexture, and demonstrated the major importance of pre-existing immunity in cancer. He developed the Immunoscore system, which is receiving wide and growing attention throughout the immuno-oncology field as a potentially more accurate system for evaluating tumors and predicting clinical outcomes, taking account of both tumor characteristics and patient immune system factors. Dr. Galon heads a worldwide task force of immunologists and pathologists from 16 countries working on clinical applications and global validation of the Immunoscore system, working together with major organizations such as the Society for Immunotherapy of Cancer (SITC) and others.
Dr. Galon’s contributions have been recognized with numerous awards, including the William B. Coley Award (NY, USA), an international prize which honors the best scientists in fundamental and cancer immunology, the Rose Lamarca Award from the Medical Research Foundation, the Gallet & Breton Award from the National Academy of Medicine, and the Simone & Cino del Duca Cancer Research Award from the National Academy of Science.
Dr. Samir N. Khleif.
Dr. Khleif is the Director of the Georgia Cancer Center, the State cancer center of Georgia at Augusta University. He is a Georgia Research Alliance Distinguished Cancer Scientist and Clinician, and a professor of Medicine, Biochemistry, Cancer Biology and Graduate Studies. He also serves as the Director of the Immuno-Oncology and Immunetherapeutics Program. Dr. Khleif previously served as Chief of the Cancer Vaccine Section at the National Cancer Institute (NCI), and Professor of Medicine at Uniformed Services University of the Health Sciences. He also served as a Special Assistant to the FDA Commissioner from 2006-2009, where he led the FDA Critical Path for Oncology designed to restructure the oncology drug development process.
Dr. Khleif’s research group focuses on the development of novel immune therapies and cancer vaccines, and rational designs for combination immune therapy, based on understanding the molecular mechanisms of the interaction between cancer and the immune system (including cancer-induced immune suppression). His team designed and conducted some of the first cancer vaccine clinical trials, and they are currently developing novel combination approaches to enhance anti-tumor effects. During his tenure at NCI, Dr. Khleif was also detailed to serve for 4 years as the Director General and CEO of the King Hussein Cancer Center in Amman, expanding and strengthening the clinical operations and building that institution into a National Comprehensive Cancer Center of Excellence. Dr. Khleif serves on the board of the Society of Immune Therapy of Cancer (SITC), and he is a member of the National Cancer Policy Forum of the National Academy of Medicine where he leads the Immunotherapy Task Force. Dr. Khleif is the chair or member of many national committees on immuno-oncology and cancer research. He is the recipient of many awards including the National Cancer Institute (NCI) Director Gold Star Award, and the Public Health Service (PHS) Commendation Medal.
Dr. John Smyth.
Dr. Smyth was appointed the first Chair of Medical Oncology in Edinburgh and, over the course of 30 years, has developed multidisciplinary oncology to create the Edinburgh Cancer Research Centre, combining laboratory and clinical research with teaching and training, and serving a population of 2 million. Dr. Smyth’s research expertise is in experimental therapeutics, from drug design through all phases of pre-clinical evaluation and clinical trials, with his major research focus on the development and evaluation of new anti-cancer drugs. He Chaired the Expert Advisory Group for Oncology & Haematology for the Commission on Human Medicines, and served for several years on the UK Committee on Safety of Medicines, as well as on the Scientific Advisory Group for Oncology for the European Medicines Agency (the Europe-wide regulatory body). Dr. Smyth also has extensive experience participating in the independent monitoring of clinical trials of checkpoint inhibitor drugs. His work has also focused on the affordability of cancer related healthcare.
Dr. Smyth has published over 300 papers and been involved in 47 books and chapters. He served as Editor-in-Chief of the European Journal of Cancer for a decade, from 2001to 2010. He is a fellow of the Royal College of Physicians of Edinburgh and London, and fellow of the Royal Society of Edinburgh, and is a past president of the European Society of Medical Oncology and the Federation of European Cancer Societies.
All in all, that is a lot of expertise guiding this trial.
Dr. Shah: So, we spoke earlier in part one of this program about some of the new research that you’re doing with DNA vaccines and conjugates with Pseudomonas toxin. Could you tell us some other interesting research you’re doing on novel therapies in neuro-oncology?
Dr. Brem: Yes. We just completed a study with Tocagen, which is a viral therapy, which will also stimulate the immune response and also uses a novel form of chemotherapy where it takes an antifungal drug that is converted genetically to an oncolytic drug. So it’s a very clever approach, and that’s a large multi-center study and that’s being analyzed right now. And we learned at this meeting that their plans to roll out a new trial through the NRG for newly diagnosed using viral therapy and we’ve heard of the poliovirus, we’ve heard of the many viral studies coming from multiple centers in Boston, Houston, and so on, and about viral therapy. And whatever the virus is, they all are oncolytic. They kill the new glioma cell, liberate new antigens, or neoantigens, which are then recognized by antigen presenting cells.
We’ve also been very active in the DCVax, which was started at UCLA but now extended to Penn and other sites. And the interesting thing of that trial, which we reported some preliminary data, is that a large percentage of the patients are now living beyond 3 years, so that is a unique approach in that the patients own tumor creates their very individual vaccine looking at their own panel of antigens. So we’re excited by that approach and we’ll be hearing more about that in the future.
Dr. Shah: Okay, so my understanding of the DCVax is that you have to take the tissue out and then generate something against the dendritic cells within that admixture.
Dr. Brem: Yes.
Dr. Shah: Could you tell us a little bit more about where that therapy stands as of now and what kind of efficacy we're getting?
Dr. Brem: Well, a very large multi-national study was concluded and so that is going to…as the data matures, that will be going to FDA. We hope that that gets approved. We don’t know, but it’s an exciting study.
Dr. Shah: Okay, so talking about getting tumor cells out and generating something against it. It seems that you are also either working on or are involved with CAR T cells in glioblastomas, so please walk us through how that works.
Dr. Brem: Well, that is an exciting effort. It’s being led at the Abramson Cancer Center by Donald O’Rourke and his team, Zed Binder. I’m involved in that group, and it has just been funded by the Abramson Cancer Center as a translational center of excellence, so there’s a huge effort underway with neurosurgery and the Parker Institute, Abramson Cancer Center, Carl June’s Laboratory, many other laboratories trying to develop the next generation of CAR T cell. So we are…we just published a first-in-man phase I human trial that showed biological activity. And now because we’re dealing with a tough foe, the glioblastoma, we’re working on potentiating this by taking down some of the tumor defenses, looking at checkpoint inhibitors, combining it, supercharging the CAR T cell vaccine in a combination therapy, so that will be the next generation. That’s the future.
Dr. Shah: So, my understanding is that perhaps part of the reason why PD-1s have not been as promising in glioblastomas is glioblastomas somehow seem to not be very rich in T cells when you sample them, so there’s something stopping them.
Dr. Brem: There’s stromal barrier and there are inhibitors like TGF-ß, IL-6, the TNF-a, there’s cytokines. Also, we’ve been very interested in looking at macrophage polarization. And I’m part of a group that published this year in Nature Communications led by Yi Fan, who presented at this meeting, showing that if you block IL-6, you could redirect the macrophage from a tumor-suppressing state, the M2 state, to the M1 immunostimulatory state, so we hope to partner with pharma on that and develop the clinical trials based on that discovery.
Dr. Shah: That is fascinating, and of course, the CAR T cell strategy makes perfect sense because you create them in vitro and then put them in.
Dr. Brem: Yeah, so ultimately, we feel by attacking the tumor microenvironment as well as creating a vaccine directed to the antigens on the tumor, we’re going to have really a new class of therapy.
