in Tumor Immunology and Cancer Immunotherapy Conference
October 2, 2020 | 8:30 a.m.—5:30 p.m.
Time Title Speaker
Neli Ulrich, PhD 8:30 a.m. Welcome Executive Director, Comprehensive Cancer Center Huntsman Cancer Institute
Antitumor Immune Responses Induced by PD-1 Antoni Ribas, MD, PhD 8:45 a.m. Blockade Therapy University of California Los Angeles
Rational Tumor and Immune Cell Treatment Daniel Peeper, PhD 9:30 a.m. Combinations: A Functional Genomics Approach Netherlands Cancer Institute
10:15 a.m. Break
Sandra D’Angelo, MD 10:30 a.m. Cancer Testis Antigens as Therapeutic Targets in Sarcoma Memorial Sloan Kettering Cancer Center
New T Cell Receptors and Targets by Dissection of Andrew Sewell, PhD 11:15 a.m. Successful Cancer Immunotherapy Cardiff University
Noon Lunch CAR T Cell-Based Combination Immunotherapy for Prasad S. Adusumilli, MD, FACS 1 p.m. Solid Tumors Memorial Sloan Kettering Cancer Center
Overcoming Resistance to Immune Checkpoint Blockers Zihai Li, MD, PhD 1:45 p.m. by Targeting GARP-TGF-Beta Pathway The Ohio State University
2:30 p.m. Break
From the Clinic to the Lab: Investigating Mechanisms of Padmanee Sharma, MD, PhD 2:45 p.m. Response and Resistance to Immune Checkpoint Therapy MD Anderson Cancer Center
The Role of Gut and Tumor Microbiome in Response Jennifer Wargo, MD, MMSc 3:30 p.m. to Cancer Therapy MD Anderson Cancer Center
4:15 p.m. Break
Ira Mellman, PhD 4:30 p.m. Mechanistic Basis of Cancer Immunotherapy Genetech
Alana Welm, PhD 5:15 p.m. Closing Remarks Co-Director, Cell Response and Regulation Program Huntsman Cancer Institute SPEAKERS
Prasad S. Adusumilli, MD, FACS Memorial Sloan Kettering Cancer Center Dr. Adusumilli is a thoracic surgeon with expertise in the management of cancers in the chest, including primary (lung cancer, mesothelioma, thymoma, esophageal cancer) and metastatic tumors. Dr. Adusumilli’s laboratory research, supported by NIH RO1 and DoD awards, focuses on tumor immunology and chimeric antigen receptor (CAR) T cell-mediated immunotherapy for cancers. Over the years, he and his lab have developed clinically relevant solid tumor mouse models and modeled regional delivery of novel biological therapies, including oncolytic viruses and immune cells in these models. This research has yielded mechanistic data that has been translated and is now in clinical trials for patients with lung cancer, mesothelioma, and breast cancer. His ongoing research focuses on combination immunotherapy to reactivate both CAR T cell and endogenous immunity by use of cell-intrinsic and extrinsic checkpoint blockade strategies; combination of CAR T cells with anti-PD1 agent is now in phase II clinical trial. As Head of solid tumor cell therapy in the Cellular Therapeutics Center at the Memorial Sloan Kettering Cancer Center, Dr. Adusumilli conducts and coordinates cell therapy clinical trials for solid tumor patients.
Sandra D’Angelo, MD Memorial Sloan Kettering Cancer Center Dr. D’Angelo is a medical oncologist at Memorial Sloan Kettering Cancer Center dedicated to developing immunotherapy for the management of sarcoma and Merkel cell carcinoma. Specifically, she is interested in understanding the efficacy of various immunotherapies and elucidating biomarkers predictive of response in patients with these rare tumors in partnerships with basic scientists, cooperative groups, and industry. Dr. D’Angelo leads the sarcoma-specific translational research program in immunotherapy at Memorial Sloan Kettering Cancer Center to systematically explore novel combination strategies with checkpoint blockade and adoptive T-cell therapy. This disease-specific work ties in, and is informed by, her role in Early Drug Development and Cellular Therapeutics Core where she participates in early phase immunotherapy studies exploring novel agents across solid tumors.
Zihai Li, MD, PhD The Ohio State University Dr. Li is the founding director of the Pelotonia Institute for Immuno-Oncology (PIIO), at the Ohio State University Comprehensive Cancer Center and is a cancer immunologist, physician scientist, and board- certified medical oncologist. Dr. Li’s research interests in the last 20 years have primarily been in the field of chaperone biology, immune tolerance, and cancer immunology, particularly related to the roles of a key immune chaperone gp96 (known also as grp94) in the endoplasmic reticulum. A leader in the field of gp96/grp94 chaperone, Dr. Li established its roles in immunity, development, and cancer by advancing the knowledge of its client network, structure-function relationship, and with co-chaperone CNPY3. He also uncovered involvement of the TGF-β-GARP axis and platelets in cancer immune tolerance and discovered CNPY2 as a key initiator of the unfolded protein response. Supported by multiple active NIH grants, Dr. Li’s lab currently focuses on developing better immunotherapeutics against cancer via understanding and reprogramming the tolerogenic tumor microenvironment. His lab has also broadened its interests toward the areas of platelet biology in cancer immune tolerance; understanding the immunological properties of heat shock proteins (HSPs) in cancer immunotherapy, innate immunity, and immune tolerance; regulatory T cells; and the unfolded protein response in inflammation and cancer. He is an elected member of the American Society for Clinical Investigation (ASCI) and the Association of American Physicians (AAP).
Ira Mellman, PhD Genentech Dr. Mellman is Vice President of Cancer Immunology at Genentech, having previously served on the Yale University School of Medicine faculty as department chair, a member of the Ludwig Institute for Cancer Research, scientific director of the Yale Cancer Center, and Sterling Professor of Cell Biology & Immunobiology. Dr. Mellman is a graduate of Oberlin and Yale, and performed postdoctoral work with Ralph Steinman at Rockefeller University. He is a member of the National Academy of Sciences, American Academy of Arts & Sciences, EMBO, and the American Association for Cancer Research Board of Directors. Dr. Mellman’s laboratory is known for advances in cell biology (including the discovery of endosomes) and for applying these insights to understanding the immune response. Of particular importance have been the elucidation of how dendritic cells initiate immunity or maintain immune tolerance, forming the basis for modern efforts in cancer vaccines. Other notable advances include demonstrating how T cell signaling is regulated by the PD-L1/PD-1 pathway, the basis of immune heterogeneity in cancer, and the conceptualization of the cancer immunity cycle. Dr. Mellman is responsible for having brought Genentech’s anti-PD-L1 antibody Tecentriq® (atezolizumab; now a marketed product) to the clinic. He also directed the discovery and early development of tiragolumab (anti-TIGIT; now in pivotal studies), iNeST-RNA (in collaboration with BioNTech; now in Phase II), cobimetinib (MEK inhibitor), mosunetuzumab (CD20-CD3 bispecific antibody), and ipatasertib (Akt inhibitor), among others. Recent awards include Yale’s highest honor, the Wilbur Cross medal, and the 2019 Leadership Award in Cancer Immunology from the American Association for Precision Medicine. SPEAKERS
Daniel S. Peeper, PhD Netherlands Cancer Institute Dr. Peeper is professor in Functional Oncogenomics VU University Amsterdam, heading the Department of Molecular Oncology & Immunology and chairing the Research Faculty Council Board at the Netherlands Cancer Institute (NKI). He set up and chaired the Translational Research Board at NKI (2014-1019). He studied Medical Biology at the VU University Amsterdam and received his PhD in the laboratory of Alex van der Eb (Leiden, 1994) for his work on adenovirus oncoproteins and cell cycle proteins. He received his postdoctoral training in the lab of Mark Ewen (Dana-Farber Cancer Institute, Harvard Medical School, Boston) and subsequently the lab of René Bernards (NKI). Previous highlights include his discoveries using functional genetics of a new metastasis gene (Nature 2004); that oncogene-induced cellular senescence (OIS) serves as a tumor suppressor mechanism limiting cancer progression in humans (Nature 2005; New Engl J Med 2006); that OIS is associated with the activation of an inflammatory transcriptome (Cell 2008; Nat Rev Cancer 2009; Genes Dev 2010); that PTEN reduction acts as an OIS bypass mechanism driving melanoma development (Genes Dev 2012); and that pyruvate dehydrogenase kinase (PDK1) acts as a critical switch for the execution of OIS (Nature 2013). His team uses function-based genetic screens to develop rational combinatorial cancer treatment, targeting both cancer and immune cells. They discovered a new mechanism mediating resistance to targeted therapy in melanoma involving the receptor tyrosine kinase AXL (Nature Comm. 2014) and established a large melanoma PDX platform with which they identified a novel resistance mechanism to BRAF inhibition (Cell Rep. 2016). Building on this finding, his laboratory developed a new rational concept for combinatorial targeting of intratumor heterogeneity, which is currently explored clinically (Nature Med. 2018). His group also dissected the mechanism of cancer drug addiction and provided PoC of how this vulnerability may be used clinically (Nature 2017). Most recently, his laboratory has been developing rational cancer treatment, combining tumor and immune cell interventions. Focusing on the interface between tumor and immune cells, his team discovered that lowering the TNF threshold sensitizes tumors to T cell attack and immunotherapy (Cell 2019). As another example, they reported the existence of pre-existing NGFR-expressing melanoma cells that display resistance to several different treatments, including T cells (Nature Comm. 2020). Several potential new tumor and immune cell drug targets have been identified and are currently being studied in preclinical models. They also emphasized the urgent clinical need to develop rational combination treatments (Mol. Cell 2020). The successful identification of new therapeutic IO targets led him to found, together with Maarten Ligtenberg and Christian Blank, an NKI spin-off company in immuno-oncology (Immagene). Dr. Peeper has received several awards, including a KWF Queen Wilhelmina Award and a Society for Melanoma Research (SMR) Outstanding Researcher Award. He is an elected Member of Oncode, EMBO, and Academia Europaea, and has been serving on the Board of the European Association for Cancer Research (EACR) since 2012.
Antoni Ribas, MD, PhD University of California Los Angeles Dr. Ribas is a professor of medicine, professor of surgery, and professor of molecular and medical pharmacology at the University of California Los Angeles (UCLA), director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center (JCCC), Director of the Parker Institute for Cancer Immunotherapy (PICI) Center at UCLA. Dr Ribas is a physician-scientist who conducts laboratory and clinical research in malignant melanoma, focusing on gene engineered T cells, PD-1 blockade, and BRAF targeted therapies. His National Cancer Institute (NCI), State of California, and foundation-supported research laboratory develops models of disease to test new therapeutic options, studies mechanism of action of treatments in patients and the molecular mechanisms of therapy resistance. He has been instrumental in the clinical development of several agents approved by the FDA, including pembrolizumab (Keytruda), vemurafenib (Zelboraf), cobimetinib (Cotellic), dabrafenib (Tafinlar), and trametinib (Mekinist). Dr. Ribas is currently the President of the American Association for Cancer Research (AACR); an elected member of the Fellows of the AACR Academy (FAACR) and the American Society of Clinical Investigation (ASCI); has a Doctor Honoris Causa from the University of Buenos Aires; co-led the Stand Up to Cancer (SU2C)-Cancer Research Institute (CRI)-AACR Immunotherapy Dream Team with the Nobel Laureate James Allison; is the recipient of a NCI Outstanding Investigator Award; was profiled as one of the five Visionaries in Medicine by the New York Times on May 27, 2018; acknowledged as Great Immigrant by the Carnegie Foundation in the New York Times on July 4, 2018; and is the recipient of the 2014 AACR Richard and Hinda Rosenthal Award, the 2018 AACR-CRI Lloyd J. Old Award in Cancer Immunology, and the 2019 William B. Coley Award in Basic and Tumor Immunology, Cancer Research Institute (CRI). SPEAKERS
Andrew Sewell, PhD Cardiff University Dr. Sewell initially trained in chemistry before undertaking a PhD in genetics at the University of Liverpool. He then embarked on postdoctoral training at the University of Utah. He still misses skiing the greatest snow on earth at Alta to this day! He returned to the UK in 1995 to research how the HIV virus evades the human immune system at the Nuffield Department of Medicine, University of Oxford, where he became a Wellcome Trust Senior Fellow. He relocated to Cardiff University in 2006 and became a Wellcome Trust Senior Investigator and has been continuously Wellcome-funded for more than 24 years. His research group focuses on T cell ligands and the receptors that recognize them (αβTCR, γδTCR, CD4, and CD8). Most of the Sewell Laboratory’s recent work is based around understanding the basic biology of antigen recognition by human T cells using novel pipelines for the discovery of new T cell targets. Collaborations with various partners have been established to develop cancer immunotherapies and have resulted in recent co-authored papers in Nature Medicine with Immunocore, Adaptimmune, and Autolus. Current research projects include dissection of successful immune responses after successful cancer immunotherapy or spontaneous remission; TCR gene transfer therapy (TCR-T); new CAR T technologies; T cell receptor-optimized peptide skewing or the repertoire of T cells (TOPSORT); artificial (non-biologic) T cell antigens as vaccines; T cell/TCR-based diagnostics in autoimmune disease; and unconventional (non-HLA-restricted) T cell responses to infection and tumors.
Padmanee Sharma, MD, PhD MD Anderson Cancer Center Dr. Sharma is a nationally and internationally renowned physician-scientist whose research work is focused on investigating immunologic mechanisms and pathways that impact tumor rejection. She is a trained medical oncologist and immunologist and the T.C. and Jeanette D. Hsu Endowed Chair in Cell Biology. Her expertise in immunology and genitourinary medical oncology enabled her to design and lead clinical trials with immune checkpoint therapy for patients with metastatic renal cell carcinoma and bladder cancer, which led to improved survival and approval of new treatments for these patients. To understand the impact of immune checkpoint therapy on human immune responses and to generate preliminary data with immune checkpoint therapy in the localized disease setting, she designed and conducted the first neoadjuvant (pre-surgical) trial with immune checkpoint therapy (anti-CTLA-4) in 2004. These studies led her to identify the ICOS/ICOSL pathway as a novel target for cancer immunotherapy strategies. Clinical trials targeting the ICOS/ICOSL pathway are currently ongoing. Dr. Sharma continues to design novel clinical trials to evaluate human immune responses to different immunotherapies and she is the principal investigator for multiple immunotherapy clinical trials that focus on translational laboratory studies. She was the first to demonstrate that human tumors express VISTA as an immunosuppressive pathway. Clinical trials targeting VISTA are currently ongoing. She was also the first to demonstrate that anti-CTLA-4 plus inhibition of EZH2 can improve anti-tumor responses, which led her to design a new clinical trial with this combination. This clinical trial is currently accruing patients. As a result of her expertise, MD Anderson Cancer Center established the Immunotherapy Platform. Dr. Sharma serves as the inaugural scientific director of the Immunotherapy Platform and she focuses her effort on a “reverse translation” process that encompasses studies on human immune responses to generate hypotheses related to mechanisms of tumor rejection, which she tests in appropriately designed pre-clinical models, and subsequently uses the new data to design novel clinical trials to improve outcomes for patients with cancer. She is a professor in the Departments of Genitourinary Medical Oncology and Immunology and is also the co-director of Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center. She is a member of the American Society for Clinical Investigation (ASCI); received the Emil Frei III Award for Excellence in Translational Research in 2016; the Coley Award for Distinguished Research for Tumor Immunology in 2018; and honored with the Women in Science with Excellence (WISE) award in 2020.
Jennifer Wargo, MD, MMSc MD Anderson Cancer Center Dr. Wargo’s career commitment is to advance the understanding and treatment of disease through science. In September 2013, Dr. Wargo joined the University of Texas MD Anderson Cancer Center after being recruited from Massachusetts General Hospital/Harvard Medical School where she obtained her medical degree and completed two fellowships at the University of California and NIH in Surgical Oncology. Dr. Wargo holds joint appointments in surgical oncology as a melanoma surgeon and genomic medicine conducting her critical research in the field of microbiome and translational research. In 2020, Dr. Wargo started a microbiome and translational research program at MD Anderson Cancer Center called PRIME TR, Program for Innovative Microbiome and Translational Research.