Southern Research – the Birmingham-based research organization specializing in drug discovery, drug development, engineering, energy and the environment– has announced the Transgenic Mouse Human PD-1/L1 Model, its newest service offering in support of immuno-oncology (IO) therapeutic development. This model could help speed the development of new cancer therapies by targeting a key checkpoint inhibitor of medicines already on the market that activate the immune system in fighting tumor cells.
“Syngeneic mouse tumor models have played a key role in the development of many of the checkpoint inhibitors currently giving patients a better chance at improved outcomes,” saidArt Tipton, Ph.D., Southern Research president and CEO. “The limitation of such models, however, is that murine versions of the therapeutic must be produced, thus the efficacy of the actual human version cannot be evaluated. Our model provides a solution.”
Southern Research is in the process of characterizing several Genetically Engineered Mouse Models (GEMMs) licensed from Nanjing Galaxy Biotech. Animals or tumors expressing the human form of PD-1/L1 or CTLA-4 will allow for evaluation of the fully human-form of checkpoint inhibitors either alone or in combination with other immune modulating agents, chemotherapeutics, oncolytic viruses or radiation.
The first of these models is ready to help speed the development of PD-1/L1 targeted therapeutics as single agents – or in combination with chemotherapeutics. The PD-1/L1 mouse is in the C57BL/6 strain with a double knock-in/out, replacing the murine PD-1 and PD-L1 with human genes. In this model, Southern Research uses the syngeneic tumor MC38 expressing human PD-L1. The system was genotyped and expression of human PD-1 and PD-L1 verified by flow cytometry analysis.
“We have completed the initial efficacy characterization with the clinical anti-PD-1 therapeutics Keytruda and Opdivo, and the anti-PD-L1 Tecentriq,” said Mike Koratich, associate director and head of Oncology for Southern Research Drug Development. “We are now confident in offering this model to the IO community.”
C57BL/6 huPD-1/L1 transgenic mice were implanted with MC38:huPD-L1 cells on Day 0. Treatment consisted of Keytruda (100 µg), Opdivo (100µg), or Tecentriq (1 mg) given on Days 3, 7, 10, and 14.
Further characterization studies are under way and focus on establishing a baseline efficacy evaluation of standard chemotherapeutics in the tumor model and to begin the exploration of checkpoint and chemotherapy combinations. These studies will also allow Southern Research to determine systemic and tumor immunology through blood/spleen immunophenotyping and characterization of tumor-infiltrating lymphocytes.
Southern Research scientists are now seeking a limited number of partners willing to allow their studies and data to be incorporated into continuing model characterization. Selected partners will get a significantly reduced rate for their study in exchange for data access, and interested academic partners are encouraged to contact the organization for next steps.
All transgenic mouse efforts fall under the Drug Development division of SR – a contract research organization committed to scientific and operational excellence in support of clients’ objectives. With expertise in bioanalytical sciences, cancer, infectious disease and toxicology, the team supports the entire drug development pipeline as well as testing of environmental and occupational hazards. Its capabilities support a wide-range of test articles including small molecules, biologics, nucleic acids, viral or viral-like vectors, antibodies, vaccines, industrial chemicals and agrochemicals. The SR Drug Development division has helped bring over half of all FDA-approved cancer drugs and approximately 90% of all anti-HIV drugs to market.
About Southern Research
Founded in 1941, in Birmingham, Alabama, Southern Research (SR) is an independent, nonprofit, scientific and engineering research organization that supports clients and partners in the pharmaceutical, biotechnology, defense, aerospace, environmental, and energy industries. SR’s staff of nearly 400 workers across four divisions: Drug Discovery, Drug Development, Engineering, and Energy & Environment. We pursue entrepreneurial and collaborative initiatives to develop and maintain a pipeline of intellectual property and innovative technologies that positively impact real-world problems. Learn more at.
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