PRE-medical Cancer Immunotherapy Network Canine Trials Network (PRECINCT)
Tumors in pet dogs arise spontaneously (as in humans), and dogs have similar genomes, immune responses, living environment, and tumor complexity to humans. Cancer clinical trials with pet dogs can provide valuable information for the development of future treatments for people. PRECINCT promotes the development of cancer immunotherapies for several common human cancers.
Background
Preclinical immunotherapy research requires reliable tumor models in animals that have fully competent immune responses and that mimic human physiology and disease. Human tumor-bearing immunodeficient mice that are common in laboratory studies are of limited use in immunotherapy studies. Although genetically engineered mice are immunocompetent, their tumors do not arise spontaneously.
Canines as a Translational Model
Canines may be a good model for understanding cancer in humans.
- Cancers in pet dogs and humans arise spontaneously.
- Dogs and humans have similar environments, genomes, immune responses, tumor complexity/heterogeneity, coevolution of the tumor microenvironment, course of disease, and treatment responses.
- Dogs have a shorter lifespan and disease progression than people, allowing for faster clinical trials.
- Researchers have the flexibility to test investigational agents in pet dogs, even in early or minimal disease states.
A New Approach in Comparative Oncology – PRECINCT 2017
In 2017, NCI granted five U01 teams and one U24 coordinating center (RFA-CA-17-001; RFA-CA-17-002) with awards to perform canine immunotherapy trials and correlative analyses to provide validation for initiating human clinical trials and ultimately determine the utility of canine cancers as predictors of human cancer therapy response. The 2017 PRECINCT was funded by the 21st Century Cures Act and promoted the development of cancer immunotherapies for several common human cancers (glioma, osteosarcoma, melanoma, and lymphoma).
The PRECINCT 2017 teams have largely completed their clinical trials and correlative studies of novel immunotherapeutics and combination therapies. One study - a losartan plus toceranib canine trial for osteosarcoma - led to a pediatric clinical trial testing a new analogous combination therapy. Canine clinical trial data from another study was included as part of a package that led to a phase I clinical trial with tumor lysate and a human version of the CD200 peptide for human patients with recurrent high grade brain tumors.
A Second Network Expands on the Efforts of the First – PRECINCT 2022
In 2022, the program was renewed with five new U01 awards (RFA-CA-21-050) as well as a single U24 for a Coordinating Center (RFA-CA-21-051). The PRECINCT 2017 and 2022 networks benefit from strong collaborations with one another and by sharing the same coordinating center at the University of Pennsylvania. The new network is covering additional areas not covered by the original including research on therapies for bladder cancer and some novel immunotherapies.
PRECINCT 2022 Goals
The PRECINCT 2022 teams are investigating diverse immunotherapies in dogs: checkpoint inhibitor, cytokine, vaccine, oncolytic virus, and adoptive CAR-iNKT cell therapies. The U01 and U24 investigators, DCTD staff, NCI intramural Comparative Oncology Program staff, and a wide range of canine cancer researchers who are funded from sources inside and outside the network attend monthly PRECINCT steering committee meetings. The network’s goals are to:
- Support canine clinical studies using immunotherapeutic agents and novel therapeutic combinations together with laboratory correlative studies that seek to describe, characterize, and understand the cellular and molecular mechanisms that determine the anti-tumor response (or non-response) in dogs with spontaneous tumors
- Include laboratories and canine clinical trial sites that will share therapeutic agents, specimens, and laboratory and clinical protocols to standardize and validate the data generated
- Support submission of canine data to the Integrated Canine Data Commons
- Develop and enhance immune cellular products modified genetically or through other manipulations for the treatment of adult and pediatric patients with solid tumors
- Support early phase clinical trials
- Explore imaging and biomarker development
- Expand our understanding of the mechanism of action as well as natural and acquired resistance to immunotherapies
PRECINCT 2022 - Funded Projects
| PIs | Lead Institution | Title |
|---|---|---|
| University of Pennsylvania | Advancing the Coordinating Center for the Canine Immunotherapy Network | |
| Mayo Clinic Rochester | Translation of a novel combination therapy approach for non-Hodgkin lymphoma | |
| North Carolina State University | Intravesical immunotherapy of spontaneous canine invasive urothelial carcinoma | |
| Deborah Knapp | Purdue University | Advancing immunotherapy through cross species studies of immune cell responses and immune checkpoint inhibitor effects in dogs and humans with invasive urinary bladder cancer |
| Nicola Mason | University of Pennsylvania | Advancing allogeneic CAR-iNKT for the treatment of solid tumors through comparative oncology |
| Tufts University | Generation of tumor specific immunity in canine osteosarcoma through dendritic cell hyperactivation |
Data Access
Data from PRECINCT 2017 and PRECINCT 2022 canine clinical trials will be made publicly available in the Integrated Canine Data Commons (ICDC).
The ICDC:
- Is a node in the larger NCI human Cancer Research Data Commons (CRDC)
- Was developed to incorporate genomic, proteomic, imaging, clinical trial, biomarker, population study, cancer model, and immuno-oncology data
- Is a resource for canine researchers to submit and access data related to cancer
- Will empower the cancer research community to generate new hypotheses that can be tested by comparative analysis in dogs and humans
- Contains clinical trial information and correlative data derived from PRECINCT, the Center for Cancer Research’s Comparative Oncology Trials Consortium (COTC), and individual canine cancer researchers
Contact
Dr. Connie Sommers (sommersc@mail.nih.gov)