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The identification and validation of new targets for antitumour immune therapy is
still a challenge for the preclinical research as the classical syngeneic tumour models
are of limited translational value and the patient derived human tumour xenograft
models (PDX) are growing on immunodeficient animals.
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
in immunodeficient mice. Twelve weeks later stable expression of lymphoid cell lineages
in peripheral blood and secondary lymphoid tissues could be detected by flow cytometry
and immunohistochemistry analysis. We investigated the co-application of cytokine
treatment (IL-3, IL-2 and IL-15) on the differentiation of immune cells. Treatment
with IL-3 increased the proliferation rate, however not the differentiation pattern.
At the time when the human immune system is developed, established melanoma PDXs were
transplanted on these humanized mice. Human tumours developed on humanized mice without
evidence of rejection. Drug-sensitivity testing with various immunoconjugates in these
tumour-bearing humanized mice will follow.
Our humanized mouse models will enable a more appropriate preclinical assessment of
immune-based therapeutic antitumour strategies especially when combining the humanized
mouse with patient-derived xenografts.
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