Immuno-oncology Discoveries, University of Chicago

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Immuno-oncology Discoveries, University of Chicago

  1. 1. Immuno-Oncology at the University of Chicago Available for download at tech.uchicago.edu/areas
  2. 2. UChicago’s Multi-faceted Approach to Immuno-Oncology The Immunology and Cancer Program at Chicago is at the forefront of discovery. Innovative, bidirectional translational research moves freely between bench and bedside. T reg Immune Stimulation Immune Checkpoint Blockade T Vaccines Diagnostics
  3. 3. New Approaches to Immune Stimulation Through the non-specific stimulation of the immune system, the host’s natural inflammatory response can halt or even reverse the growth of tumors. These novel technologies allow for the treatment of both primary solid tumors and metastases. T Activation/ Clonal expansion Proinflammatory Cytokine production Chemokines & Adhesion molecules Microphage/granulocyte activation T TCR TLR MHC Stromal cells Inflammation Self tissue destruction T reg IL-2 Recruitment of immune cells Altered microenvironment Autoimmunity Autoantibody production Representative Technologies Yang-Xin Fu, MD, PhD • LIGHT is a TNF family member that enhances the immune response to tumor cells by augmenting the recruiting and priming of naïve T cells specific to a variety of tumor antigens. • LIGHT eradicates established, aggressive tumors (both primary and metastatic) in murine models. • LIGHT establishes immune memory to protect against future challenge with tumor cells. • LIGHT-antibody conjugations are a platform for the creation of a variety of targeted anti-cancer therapeutics. Thomas Gajewski, MD, PhD • Dr. Gajewski has identified new methods of stimulating T-cells for recognition of tumor cells through unique molecules and diverse pathways. • Several novel mechanisms for immune recognition have been identified and characterized in mouse models. • These new pathways are targets for developing immunotherapies that can be used to reactivate patient immune systems to better treat tumors.
  4. 4. Immune Checkpoint Blockade Immune checkpoints are known to be altered towards cancerous cells, preventing native T-cells from generating an effective response. Reversing these blockades results in new approaches to effectively treat cancers alone or in a combinatorial regimen. Anergy T DGK inhibitor Tumor cell Representative Technologies Thomas Gajewski, MD, PhD • Methods of using DGK inhibitors and analogs to alleviate T-cell anergy for the treatment of cancer. • T-cell anergy has been reversed using small molecule DGK inhibitors in mouse models. • DGK inhibition is a novel immunotherapeutic method that can be used as an adjuvant to leverage an immune response in anergic tumors. Possible first indications include melanoma and breast cancer. T Tumor cell
  5. 5. Immunotherapy Vaccines The power of the immune system can be harnessed to mount an anti-cancer response. Tumor antigen vaccines built using synthetic proteins or peptides, or encoded by a plasmid or virus, can evoke an endogenous T cell response, leading to tumor cell recognition and an anti-cancer immune response. Adeno-LIGHT Senescence inducing compounds T Tumor Representative Technologies Stephen J. Kron, MD, PhD • An antitumor immune response to the primary tumor and/or to gross metastases is generated by a tumor-derived senescent cell vaccine. • In an immuno-competent mouse model, this senescent cell approach promotes reduction of volume in sites distant to injection, and can act prophylactically. • The use of oncosenescence is an innovative means to evoke an effective self-immune response in prostate cancer patients. Hans Schreiber, MD, PhD • Optimized sequences for novel antibodies that specifically identify cancer cells via abnormally glycosylated protein epitopes have been developed. • In vivo POC of several of these antibody sequences in a mouse Chimeric Antigen Receptor T cell (CART) model showed strong anti-tumor activity. • These optimized antibody sequences can be built into existing therapeutic backbones, such as CARs and BiTES, to generate broadly effective, novel anticancer agents.
  6. 6. Immunotherapy Diagnostics Cutting edge DNA and protein diagnostics can identify patients who need particular immunotherapies in order to have a successful anti-cancer response to therapy. These diagnostic markers can also include new targets for development of additional immunotherapies. Representative Technologies Yusuke Nakamura, MD, PhD • Dr. Nakamura is a leader in genomic research, with a proven track record in discovery and cancer. • Current efforts include large scale screening capabilities and a focus on identifying key biomarkers involved in the immune response to cancer. • Identification of critical immunotherapy biomarkers will create an opportunity for effective personalized medicine strategies for cancer patients. Thomas Gajewski, MD, PhD • An EGR2-based gene signature differentiates between immune responsive and non-responsive tumors. • Validated studies comparing gene expression profiling have identified a key set of genes involved in the immune response to cancer. • This diagnostic would be useful for identification of patients in need of immune-stimulating therapy to facilitate the successful treatment of cancers.
  7. 7. The University of Chicago Medicine Comprehensive Cancer Center (UCCCC) At the forefront of discovery, where innovative, bidirectional translational research moves freely between bench and bedside. Clinical Trials Capabilities • Over 320 active therapeutic clinical trials, spanning preclinical to investigator –initiated phase I trials, to phase II trials in regional network, to phase III studies within Alliance • Leader and participant in regional and national clinical trial networks • Areas of expertise include: • First-in-human studies (phase I trials) • Combination and drug-drug interaction studies • Food-effect studies • Organ dysfunction studies • Population pharmacology and pharmacogenetics • Innovative trial designs • Pharmacodynamic biomarker studies Core Facilities • • • • • • • • • • • • • Biostatistics Cancer Clinical Trials Office Cytometry and Antibody Technology Genomics Human Immunologic Monitoring-cGMP Human Tissue Resource Center Image Computing, Analysis, and Repository Integrated Microscopy Integrated Small Animal Imaging Research Pharmacology Transgenic Mouse and Embryonic Stem Cell Facility Center for Research Informatics (CRI) Bioinformatics Epidemiology and Research Recruitment The Immunology and Cancer Program* Program Leader: Thomas F. Gajewski, MD, PhD • 22 member multi-department effort to identify novel immunotherapies for the treatment of cancer. • Program leaders aim to understand the interface between the immune system and malignant tumors and, ultimately, manipulate that interaction to promote immune – mediated tumor destruction in patients with cancer. Goals include: • Fundamental investigations in immunology that have relevance to the cancer context. • Preclinical models of antitumor immunity. • Translation of fundamental research discoveries into clinical studies of human antitumor immunity and novel immunotherapy clinical trials. *This program represents one of the UCCCC’s six dedicated research programs.
  8. 8. Available Immunotherapy Technologies Immune Stimulation • LIGHT for the treatment of primary tumors and metastatic disease: Conjugation of LIGHT to tumor-targeting antibodies or other immunogenic molecules presents a platform opportunity in which a variety of targeted anticancer therapeutics can be created to effectively treat both primary and metastatic disease. Immune Checkpoint Blockade • Immune response regulation for the treatment of cancer and autoimmune disorders: Downregulation of DGK using small molecule inhibitors alleviates T-cell anergy, allowing the immune system to mount a defense against cancer cells. Vaccines • A senescent cell vaccine induces an anti-tumor immune response: This vaccine derived from tumors promotes reduction of volume in distant metastases, and can act prophylactically. • Novel cancer-specific, optimized antibody sequences for use in adoptive immunotherapy: Novel antibodies developed against cancer specific epitopes resulting from defective O-linked glycosylation, for use in adoptive immunotherapy for the treatment of primary tumors and distant metastases. • LIGHT for the treatment of primary tumors and metastatic disease: Adeno-viral delivered protease-resistant LIGHT is effective in the recruitment of an immune response to tumors and leads to eradication of both primary tumors and distant metastases. Diagnostics • A new diagnostic for the identification of patients in need of an immune-stimulating anti-cancer therapy: An EGR2-based gene signature differentiates between immune responsive and non-responsive tumors.
  9. 9. How to Partner with the University of Chicago Contact UChicagoTech, the Center for Technology Development & Ventures, to learn more. We build strong industry partnerships to successfully bring innovation to the marketplace. UChicagoTech can connect you to emerging technologies and fieldadvancing researchers that may inform and enrich your own innovation efforts. We value your involvement at every stage of the invention pipeline, from idea to tangible asset. For more information, visit us at tech.uchicago.edu or contact anyone on the Oncology team. Steven Kuemmerle, PhD Deputy Director Phone: 773-834-3211 skuemmerle@tech.uchicago.edu Divya Varshney, MBA Chief Marketing Officer Phone: 773-702-8696 dvarshney@tech.uchicago.edu cancer.uchicago.edu Thelma Tennant, PhD Project Manager Phone: 773-834-4020 ttenant@tech.uchicago.edu

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