Models now availableContact
Southern Research is pleased to announce our newest service offerings in support of immuno-oncology therapeutic development.
We are in the process of characterizing several Genetically Engineered Mouse Models 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.
About the Model
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 the human genes. In this model we use 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 (see Relevant Data). We are now offering our transgenic human PD-1/L1 model to the immuno-oncology community.
Further characterization studies of the human PD-1/L1 GEMM are underway and are focused 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 us to determine systemic and tumor immunology through blood/spleen immunophenotyping and characterization of tumor-infiltrating lymphocytes (TILs).
In vivo efficacy evaluation of immuno-oncology therapeutics relies on using model systems with an intact immune system. For this reason syngeneic mouse tumor models have played a key role in the development of many of the checkpoint inhibitors that are currently providing better outcomes for many patients.
Syngeneic mouse tumor models have proven valuable in discovering checkpoint inhibitors. A limitation of the syngeneic models is the requirement that murine versions of the therapeutic must be produced. This limitation means that the efficacy of the actual human version cannot be evaluated directly in murine efficacy models. This observation becomes particularly problematic when exploring currently marketed checkpoint inhibitors used in combination with standard chemotherapeutic agents.
Our human PD-1/L1 transgenic mouse model allows for the fully human version of the PD-1 or PD-L1 therapeutic to be evaluated. This includes any of the currently approved PD-1 and PD-L1 checkpoint therapeutics. The advantages of this model are particular exciting for exploration of combination therapeutic approaches.
C57BL/6 huPD-1/L1 transgenic mice were implanted with MC38:huPD-L1 cells on Day 0. Treatment consisted of Keytruda (100 µg), Opdivo (100 µg), or Tecentriq (1 mg) given on Days 3, 7, 10, and 14.