Create an Adult Immunotherapy Network
NCI has announced several funding opportunities that align with the Cancer Moonshot.See Funding Opportunities
Immunotherapy leverages the ability of the immune system to recognize and destroy infected, damaged, and abnormal cells. This type of cancer treatment trains and augments immune cells to recognize and kill cancer cells by distinguishing them from normal cells. However, several challenges need to be addressed to improve the effectiveness of immunotherapy.
While there has been some promising success in treating certain cancers with immunotherapy, it has been less effective for other cancers. Safely and effectively targeting cancer cells without harming normal tissues is often more difficult in solid tumors than blood and bone cancers. The tumor’s microenvironment may also suppress the immune system, limiting its ability to fight off the cancer.
This Cancer Moonshot recommendation is focused on developing new immunotherapies, improving the effectiveness of current immunotherapy treatments, and creating vaccines that will prevent new cancer cases to reduce the burden of cancer in adults.
The Immuno-Oncology Translational Network (IOTN)
The collaborative Immuno-Oncology Translational Network is working to accelerate the discovery of new immune targets for cancer treatments and the development of new immunotherapies to treat and prevent adult cancers.
Researchers working on IOTN Immunotherapy Research Projects are investigating interactions between tumors and the immune system, identifying new targets for immunotherapies, examining the development of resistance to immunotherapies, and testing new immunotherapies in preclinical studies. IOTN Immunoprevention Research Projects are identifying targets for immunoprevention approaches in pre-cancers and designing early interventions, like cancer vaccines, to prevent high-risk adult cancers in adults. Researchers working on IOTN Research Projects for Mitigating Immune-Related Adverse Events are investigating ways to eliminate or reduce harmful side effects caused by immunotherapies.
Investigators with the IOTN Immuno-Engineering to Improve Immunotherapy (i3) Centers are using bioengineering and systems biology approaches to design more effective, safer, and broadly available immunotherapies.
The network includes a Cellular Immunotherapy Data Resource (CIDR) that collects information about patients receiving cell-based immunotherapies, which can inform future studies of immunotherapeutic treatments. The IOTN Data Management and Resource Sharing Center (DMRC) supports the data analysis needs of the IOTN, promotes collaboration between IOTN investigators, and outreach of the network to the cancer research community. In addition to their work with the IOTN, the DMRC facilitates the Cancer Moonshot Seminar Series.
Highlights of IOTN Research Progress
One IOTN research team developed models integrating clinical and molecular data to predict whether patients with prostate cancer will develop resistance to immunotherapy.
Another IOTN study found a combination therapy that reduces immune-related adverse events (irAEs) associated with immune-checkpoint blockade therapy in patients with solid tumors.
The IOTN CIDR collects data on long-term outcomes of patients receiving cellular immunotherapies and makes it available to the research community to inform observational, preclinical, and clinical studies. In response to the SARS-CoV-2 pandemic, the CIDR rapidly modified its forms to collect data and clinical outcomes of COVID-19 infections among transplant and cell therapy patients.
More information about the network can be found on Twitter at @IOTNmoonshot.
NCI Center for Cell-Based Therapy (CCT)
NCI created a Center for Cell-Based Therapy to focus on the use of living immune cells for cancer immunotherapies. Its mission is to support the discovery and development of new cellular immunotherapies to treat patients with cancer. The center is performing basic research of cell-based cancer therapies, accelerating the translation of cell-based immunotherapy findings to the clinic, training scientists to conduct immunotherapy studies, and providing cancer researchers with access to immunotherapy-related technologies.
Cancer Immune Monitoring and Analysis Centers (CIMACs) and the Cancer Immunologic Data Commons (CIDC)
Together, the four Cancer Immune Monitoring and Analysis Centers (CIMACs) and the Cancer Immunologic Data Commons (CIDC) form the multidisciplinary CIMAC-CIDC network. The network is addressing the critical importance of biomarkers in the management of cancer patients receiving immunotherapy. Each CIMAC consists of a multidisciplinary group of scientists with basic, translational, clinical, and computational research expertise. CIMACs are providing a wide range of state-of-the-art analyses to characterize the responses of patients in the NCI-funded early-phase immunotherapy trials using validated and standardized platforms.
The CIDC facilitates network activities including optimizing data collection methods for immune-related biomarkers, integrating data from immunotherapy clinical trials, and building a biomarker database for use by the immuno-oncology community.
Together with a public-private research collaboration called Partnership for Accelerating Cancer Therapies (PACT), the CIMAC-CIDC network is supporting immunology biomarkers assays for more than 40 trials run by NCI national clinical trial networks and pharmaceutical companies. The assays are being used to characterize responses in patients treated in these clinical trials. PACT also facilitates information sharing across government, academia, and industry.
Pancreatic Cancer Microenvironment Network (PaCMEN)
The Pancreatic Cancer Microenvironment Network was created to conduct research to improve therapeutic outcomes for patients with pancreatic cancer, which is the third most common cause of cancer-related death in the United States. In-depth studies of the pancreatic tumor micronevironment can lead to discoveries of vulnerabilities that could be exploited by immunotherapies.
For example, in one PaCMEN study, drugs called angiotensin receptor blockers, which are commonly used to treat hypertension, were shown to modify the tumor microenvironment and enhance the effectiveness of immunotherapy in mice. This research has been translated into two clinical trials for patients with pancreatic cancer (NCT03563248, NCT01821729), leading to remarkable clinical responses.
Another group successfully translated their studies to an early-phase combination trial (NCT04161755) with immune checkpoint blockade, chemotherapy, and mRNA neoantigen vaccination in patients with pancreatic cancer.
PRE-medical Cancer Immunotherapy Network Canine Trials (PRECINCT)
PRECINCT researchers evaluate next-generation immunotherapies and combination immunotherapies in canine patients, which provides not only more effective treatments for these pets but also important insights that could improve the lives of their human counterparts. PRECINCT investigators are conducting canine clinical trials in pet dogs with osteosarcoma, lymphoma, melanoma, and glioma. Two of the canine clinical trials have yielded such encouraging results that early-phase human clinical trials have been initiated for children with osteosarcoma (NCT03900793) and adults with glioblastoma (NCT04642937).
Adult Immunotherapy Projects Awarded Cancer Moonshot Funding
|Funding Opportunity||Project Title||Institution||Principal Investigator(s)|
|Immuno-Oncology Translational Network (IOTN): Cancer Immunotherapy Research Projects (U01)||Enhancing Cell Therapy for Brain Tumors||Children's Research Institute||Bollard, Catherine M; Cruz, Conrad Russell Young; Jones, Richard J; Savoldo, Barbara|
|B Cell-Dependent Anti-Tumor Immunity in Ovarian Cancer||H. Lee Moffitt Cancer Center & Research Institute||Conejo-Garcia, Jose R|
|N-Glycosylation and Immunotherapy for Cancer||University of California - Irvine||Demetriou, Michael|
|Immunosuppressive Mechanisms Responsible for Development of Non-Viral Liver Cancer and Control of its Response to Immune Checkpoint Inhibitors||University of California - San Diego||Karin, Michael; El-Khoueiry, Anthony Boutros; Tsukamoto, Hidekazu; Shalapour, Shabnam|
|Muc1-C is a Target for Reversing Immune Evasion and Resistance to Immunotherapies||Dana Farber Cancer Institute||Kufe, Donald W; Wong, Kwok Kin|
|Immunomodulation of the Tumor Microenvironment with Molecular Targeted Radiotherapy to Facilitate an Adaptive Anti-Tumor Immune Response to Combined Modality Immunotherapies||University of Wisconsin - Madison||Morris, Zachary Scott; Weichert, Jamey P|
|Stimulating Neo-Antigen Specific T Cell Responses in Head and Neck Cancers||La Jolla Institute for Allergy & Immunology||Schoenberger, Stephen Philip; Gutkind, J Silvio; Rao, Anjana|
|Targeting the Immunosuppressive Tumor Microenvironment to Enhance Efficacy of Radiotherapy and Immuno-radiotherapy for Oral Cancer||Baylor College of Medicine||Sikora, Andrew Gregory; Annapragada, Ananth V|
|Molecular and Immune Drivers of Immunotherapy Responsiveness in Prostate Cancer||Dana Farber Cancer Institute||Van Allen, Eliezer M; Fong, Lawrence|
|Targeting Alternative Splicing for TCR Discovery in Small Cell Carcinomas||University of California - Los Angeles||Witte, Owen N; Crooks, Gay M; Xing, Yi|
|Epithelium-derived Alarmins Role in Breast Cancer Immunoprevention||Massachusetts General Hospital||Demehri, Shadmehr|
|Neoantigen Vaccination for Lynch Syndrome Immunoprevention||Weill Medical College of Cornell University||Lipkin, Steven M; Vilar-Sanchez, Eduardo|
|Immuno-Oncology Translation Network (IOTN): Data Management and Resource-Sharing Center (DMRC) (U24)||Immuno-Oncology Translation Network: Data Management and Resource-Sharing Center at RPCI||Roswell Park Cancer Institute||Hutson, Alan David; Liu, Song; Morgan, Martin T; Odunsi, Kunle O|
|Immuno-Oncology Translation Network (IOTN): Cellular Immunotherapy Data Resource (CIDR) (U24)||Immuno-Oncology Translation Network (IOTN): Cellular Immunotherapy Data Resource (CIDR)||Medical College of Wisconsin||Horowitz, Mary Maresca|
|Canine Immunotherapy Trials and Correlative Studies (U01)||Canine Immuno Neurotherapeutics||University of Alabama at Birmingham||Chambers, M.R.|
|Enhancing the Efficacy of Immunotherapy in DLBCL using Rational Combination Approaches||Tufts University||London, Cheryl A; Richards, Kristy L|
|Novel Combined Immunotherapeutic Strategies for Glioma: Using Pet Dogs as a Large Animal Spontaneous Model||University of Minnesota||Pluhar, Grace Elizabeth|
|Enhancing Natural Killer Immunotherapy with First-in-Dog Trials of Inhaled Recombinant IL-15 and Super-agonist IL-15 in Naturally Occurring Canine Cancers||University of California at Davis||Canter, Robert; Rebhun, Robert|
|Optimizing Novel Immunotherapy Combinations Targeting the Tumor Microenvironment in Canine Spontaneous Osteosarcoma||Colorado State University||Dow, Steven W; London, Cheryl A|
|Coordinating Center for Canine Immunotherapy Trials and Correlative Studies (U24)||Coordinating Center for Canine Immunotherapy Trials and Correlative Studies||University of Pennsylvania||Mason, Nicola J; Propert, Kathleen Jjoy|
|Consortium for Pancreatic Ductal Adenocarcinoma (PDAC) Translational Studies on the Tumor Microenvironment (U01)||Interrupting Cellular Crosstalk in the Immunosuppressive Microenvironment of Pancreas Cancer||University of Michigan||Crawford, Howard C; Pasca Di Magliano, Marina|
|Systematic Interrogation of the Pancreatic Cancer Microenvironment in Patient-Derived Specimens||Dana-Farber Cancer Institute||Hahn, William C|
|Defining Neoantigen Immunodominance for Antigen Selection and Biomarker Discovery in Human Pancreatic Cancer Immunotherapy||Sloan-Kettering Institute for Cancer Research||Balachandran, Vinod P; Leach, Steven D|
|Disrupting the Immune and Drug-Privileged Microenvironment in Pancreas Cancer||Fred Hutchinson Cancer Research Center||Hingorani, Sunil R|
|Reprogramming Pdac Tumor Microenvironment to Improve Immunotherapy||Massachusetts General Hospital||Jain, Rakesh K; Pittet, Mikael|
|Resource Center for the Consortium for Pancreatic Ductal Adenocarcinoma (PDAC) Translational Studies (U24)||Pancreatic Ductal Adenocarcinoma Translational Resource Center (Patrec)||University of Texas MD Anderson Cancer Center||Wistuba, Ignacio I; Maitra, Anirban|
|Metabolic Reprogramming to Improve Immunotherapy (R01)||Directing the Metabolic Fate of CAR T Cells||University of Pennsylvania||June, Carl H|
|Metabolic Reprogramming of Tregs in Tumor Immunity||St. Jude Children’s Research Hospital||Chi, Hongbo|
Network (IOTN): Cancer Immunoprevention Research Projects (UG3/UH3)
|Intercepting progression from pre-invasive to invasive lung adenocarcinoma||Weill Medical College of Cornell University||Altorki, Nasser Khaled; Borczuk, Alain C; Elemento, Olivier ; Mcgraw, Timothy E; Mittal, Vivek|
|Recurrent Tumor-Specific Alternately Processed Transcripts as a Source of Neoantigens for NF1-associated Malignant Peripheral Nerve Sheath Tumor Immunoprevention||University Of Minnesota||Largaespada, David Andrew|
Network (IOTN): Immuno-engineering to Improve Immunotherapy (i3) Centers (U54 Clinical Trial Not Allowed)
|Nano-Immuno-Oncology Approaches to Overcome Tumor Immune Evasion||UT Southwestern Medical Center||Gao, Jinming|
|Engineering the Next Generation of T Cells||University Of Pennsylvania||June, Carl H|
|UCSF Center for Synthetic Immunology: Tools to Reprogram the Immune System to Combat Cancer||University Of California, San Francisco||Lim, Wendell A|
|Biomaterials to Create T Cell Immunity||Harvard University||Mooney, David J; Hodi, Frank S|
Network (IOTN): Cancer Immunoprevention Research Projects (U01 Clinical Trial Not Allowed)
|Robust Immuno-prevention Strategies for High-Risk Oral Epithelial Dysplasia||University Of Michigan At Ann Arbor||Lei, Yu Leo; Brenner, John Chadwick; Neamati, Nouri|
Network (IOTN): Cancer Immunotherapy Research Projects (U01 Clinical Trial Not Allowed)
|Mechanisms of Exosome Driven Immunoregulation of Cancer Progression||University Of California, San Francisco||Blelloch, Robert; Fong, Lawrence|
|Cytokine immunotherapies for melanoma||Yale University||Bosenberg, Marcus W; Ring, Aaron Michael|
|Human CD3epsilon co-potentiation to boost immunotherapy||University Of Missouri-Columbia||Gil Pages, Diana|
|Optimizing myeloma-specific immunity after autologous stem cell transplantation||Fred Hutchinson Cancer Research Center||Hill, Geoffrey Roger|
|Reprograming the tumor microenvironment to overcome multiple primary and acquired immune resistance mechanisms in ovarian cancer||Roswell Park Cancer Institute Corp||Odunsi, Kunle O; Gambotto, Andrea ; Kozbor, Danuta B|
|Defining mechanisms of immunotherapy resistance in head and neck squamous cell carcinomas||Dana-Farber Cancer Inst||Uppaluri, Ravindra; Barbie, David A; Haddad, Robert I|
|Cancer Immune Monitoring and Analysis Centers (CIMACs) (U24)||High-Dimensional Immune Monitoring of NCI-Supported Immunotherapy Trials||Icahn School of Medicine at Mount Sinai||Gnjatic, Sacha|
|Immune Monitoring and Analysis of Cancer at Stanford (IMACS)||Stanford University||Maecker, Holden; Bendall, Sean Curtis|
|Translational Cancer Immune Monitoring and Analysis Center (TCIMAC)||University of Texas MD Anderson Cancer Center||Wistuba, Ignacio I.; Al-Atrash, Gheath; Bernatchez, Chantale|
|Cancer Immune Monitoring and Analysis Center||Dana-Farber Cancer Institute||Wu, Catherine Ju-Ying; Hodi, Frank S.|
|Cancer Immunologic Data Commons (CIDC) (U24)||Cancer Immunologic Data Commons||Dana-Farber Cancer Institute||Liu, Xiaole Shirley; Cerami, Ethan|
|Advancing Cancer Immunotherapy by Mitigating Immune-Related Adverse Events (irAE) (U01)||Engineering Immunotherapeutic Probiotics to Mitigate irAE||Columbia University New York Morningside||Danino, Tal|
|Identification of Pathways to Mitigate Immune-Related Adverse Events with Cancer Immunotherapy||National Jewish Health||Leung, Donald YM; Kern, Jeffrey A; Lacouture, Mario|
|Finding the Optimal Balance of Immunotherapy Efficacy and Toxicity||UT Southwestern Medical Center||Gerber, David Eric; Wakeland, Edward K; Xie, Yang|
|Characterizing and Predicting Colitis in immune Checkpoint Blockade-Treated Cancer Patients||Icahn School of Medicine at Mount Sinai||Gnjatic, Sacha; Colombel, Jean-Frederic; Faith, Jeremiah James|