Therapeutics


To best replicate the appropriate treatment envi- ronment, animal models must provide the neces- sary molecular signals intrinsic to the disease micro-environment, and also provide sufficient viability factors to complement the evolutionary requirements for human cell functions working within the context of


the rodent host.


Understanding which cytokines are sufficient for functions and those that are necessary tonic sig- nals to keep human cells at homeostasis are major parts of reassembling the host micro-environment suitable for efficacy testing. Work from the Nilsson lab demonstrated that advanced models for testing T-cell therapies could reveal new insights into how CAR-T and adoptive cell thera- pies can be tested and leveraged to optimal patient outcomes, but the impact applies to other immune cell types with similar requirements. Researchers at the Central Institute for


Experimental Animals (CIEA) in Japan have taken this fundamental requirement and extrapolated it


Drug Discovery World Spring 2018


to other immune cell types. The CIEA has long been invested in the iterative development of ani- mal models to create an optimal host environment for human cell engraftment. Thus far, CIEA researchers demonstrated that


supportive


cytokines expressed endogenously are necessary and sufficient to sustain long-term viability of sev- eral important innate and adaptive immune cell lineages, including myeloid suppressor cells2, B cells3, dendritic cells4 and NK cells. In particular, the need for novel systems to


exploit NK cell biology has been addressed. Previously, NK cell engraftment into immune- deficient hosts has been limited by poor uptake and short viability, making them particularly dif- ficult to study in vivo. Katano et al at the CIEA recently demonstrated that a mouse model expressing the crucial cytokine interleukin 15 (IL-15) can rescue NK cell engraftment and sur- vival sufficient to test applications in oncology5. Taken together, this research suggests that as new


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