Applications of the Pan hCD3 mouse model
Efficacy studies
Due to its unique characteristics, the Pan hCD3 strain is a useful model for the evaluation of new T-cell engagers (TCE), both in the context of cancer studies or for the treatment of autoimmune diseases. As it is shown it the graph on the right, treatment of Pan hCD3 mice with a bispecific antibody (BsAb) targeting both CD3 and a tumor associated antigen (TAA) leads to a marked reduction of tumor growth, which is not observed in mice treated with the control BsAb.
To test the efficacy of their T-cell engager in an immunocompetent mouse model, AstraZeneca employed a syngeneic humanized Pan CD3 model implanted with MC38-TAA cells. They were able to show that their bispecific TCE has strong antitumor activity (see figure below), proving that this model can be used for efficacy studies of new immunotherapies.
▶ For more information, check out AstraZeneca’s poster here
Safety studies
The Pan hCD3 model was also shown to be a useful tool for safety studies, as demonstrated by the induction of the cytokine release syndrome (cytokine release and body weight loss) upon OKT-3 treatment (see figure below):
▶ For more information, check out genOway’s poster here
What sets the Pan hCD3 mouse model apart?
With our partners from the pharma industry, we have established that:
- The Pan hCD3 displays a physiological expression of human CD3
- CD3-targeting agents (mono- and bispecific) induce the proliferation of T cells and cytokine/chemokine secretion in the Pan hCD3 model, suggesting a stable and functional CD3/TCR complex
- Upon OVA or KLH vaccination, the level of secreted IgM and IgG is similar to WT mice, indicating a functional T/B-cell cooperation
- Several immune parameters, including thymic development of T cells and distribution of their subsets in the spleen, were compared to those in WT mice and showed no alteration
New humanized Pan CD3 model to assess T-cell engagers
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