Immuno-oncology Discoveries, University of Chicago
Immuno-Oncology at the University of Chicago
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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.
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
Self tissue destruction
Recruitment of immune cells
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
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
• These new pathways are targets for developing
immunotherapies that can be used to reactivate
patient immune systems to better treat tumors.
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.
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
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
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
• 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
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
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
• Identification of critical immunotherapy
biomarkers will create an opportunity for effective
personalized medicine strategies for cancer
Thomas Gajewski, MD, PhD
• An EGR2-based gene signature differentiates
between immune responsive and non-responsive
• 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.
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
• Areas of expertise include:
First-in-human studies (phase I trials)
Combination and drug-drug interaction studies
Organ dysfunction studies
Population pharmacology and pharmacogenetics
Innovative trial designs
Pharmacodynamic biomarker studies
Cancer Clinical Trials Office
Cytometry and Antibody Technology
Human Immunologic Monitoring-cGMP
Human Tissue Resource Center
Image Computing, Analysis, and Repository
Integrated Small Animal Imaging Research
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.
• 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
*This program represents one of the UCCCC’s six dedicated research programs.
Available Immunotherapy Technologies
• 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
• 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.
• 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.
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