Southern Research announced that it is offering researchers a new transgenic mouse model to speed the development of new cancer therapies targeting a key pathway used in medicines already on the market to activate the immune system in fighting tumor cells.

Southern Research’s Drug Development division is offering the Transgenic Mouse Human PD-1/L-1 Model to support the development of immune-oncology (IO) therapeutics, a promising new avenue of treatment focusing on a protein checkpoint associated with tumor survival.

“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,” said Art 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,” he added.

Southern Research is in the process of characterizing several Genetically Engineered Mouse Models (GEMMs) licensed from Nanjing Galaxy Biotech.

Southern Research
Mike Koratich is associate director and head of Oncology for Southern Research Drug Development.

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, other immunotherapies, or radiation.

PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as an “off switch” that keep T cells from attacking other cells in the body. When PD-1 binds to the PD-L1 protein, it instructs the T cell to leave the other cell alone.

Some cancer cells have large amounts of PD-L1, helping them evade immune attack, according to the American Cancer Society.

Blocking this reaction is the goal of new monoclonal antibody medicines, which stimulate the immune system to fight tumor cells.

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.”

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.

The Drug Development division possesses expertise in bioanalytical sciences, cancer, infectious disease and toxicology. The team supports the entire drug development pipeline as well as the 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 Drug Development division has helped bring over half of all FDA-approved cancer drugs and approximately 90 percent of all anti-HIV drugs to market.