Backgrounds: Fighting cancer by taking advantage of a patient's own immune system is showing considerable success in oncology research. Using therapeutic antibodies against tumor-associated antigens or modulating the host immune system, has been shown to prolong survival of patients with certain solid tumors or leukemia, particularly when combined with conventional treatments. Recent fast-track designations and regulatory approvals (including the first FDA approvals of anti-PD-1 agents in advanced melanoma) have signified the coming of age of cancer immunotherapy as a treatment paradigm, creating both potential patient benefits and commercial success for the pharmaceutical industry. A lack of experimental immunotherapy models is a major obstacle toward answering these questions and developing better treatments, and there is a high unmet need for new preclinical models to help drive forward immune therapy research and to recapitulate clinical treatments.
Results: Crown Bioscience has created transient human immunity in mice (MiXeno) for testing human immunotherapeutics, particularly T cell engaged immunotherapies by mixing human peripheral blood mononucleated cells (PBMC) with xenograft models. Our data showed that anti-human PD-1 or PD-L1 antibodies demonstrated significant anti-tumor activities in several Mixeno models, including A375 melanoma model and KARPAS-299 lymphoma model. The emergence of the efficacy coincided with the T cell reconstitution in mouse blood. T cells are also recruited to the tumor microenvironment. The number of T cells in the tumor microenvironment varies significant and is largely dependent on tumor cells itself.
Conclusion: The MiXeno model provides an alternative to the full stem cell reconstitution approach, and may allow T cell engaged immunotherapies (monotherapies or combinational therapies) to be evaluated in xenograft models.
Citation Format: Juan Zhang, Meng Qiao, Qian Shi. Using MiXeno Mouse Models as Robust Tool to Evaluate T Cell Dependent Immunotherapies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-B12.