The identification and validation of new targets for antitumor immune therapy is still a challenge for the preclinical research as the classical syngeneic tumor models are of limited translational value and patient-derived human tumor xenograft models (PDX) are growing on immunodeficient animals.
To overcome these constraints our aim is the development of PDX models on mice with a functional human immune system to improve predictability of drug efficacy and safety.
We reconstituted a human immune system by engrafting human hematopoietic stem cells isolated from cord blood in immunodeficient mice. A stable expression of lymphoid cell lineages in peripheral blood and secondary lymphoid tissues could be detected by flow cytometry and immunohistochemistry analysis.
At the time when the human immune system is developed, established patient-derived tumors were transplanted on these humanized mice. Human tumors developed on humanized mice without evidence of rejection. Tumors from different tumor entities grow on humanized mice with a similar level of engraftment compared to not-humanized mice.
We also tested the effect of ipilimumab (anti-CTLA-4 [cytotoxic T-lymphocyte antigen-4] mAB) and the humanized monoclonal antibody herceptin in these tumor-bearing humanized mice. We found ipilimumab could lead to a slight tumor growth delay and an increased percentage of T-cells in the blood and in the tumor.
Initially results revealed that our humanized mouse models could enable a more appropriate preclinical assessment of immune-based therapeutic antitumor strategies especially when combining the humanized mouse with patient-derived xenografts.
Citation Format: Annika Wulf-Goldenberg, Maria Stecklum, Iduna Fichtner, Jens Hoffmann. Preclinical model of patient-derived tumor transplant in humanized mice for cancer immunotherapy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B118.
- ©2016 American Association for Cancer Research.