Despite the convenience and appeal of oral therapies, the reality is that immunotherapies cannot be effectively administered by mouth due to the undesirable breakdown of important immunologically active proteins that would occur in the gastrointestinal (GI) tract. In particular, research shows that vaccine-based immunotherapy treatments are best administered via skin injections. However, until now researchers have really lacked an appropriate murine model to study human skin immunity in vivo.

 

As a major immunological organ with the ability to capture pathogens through endocytic pathways and exhibiting cross-presentation ability, the skin tissue plays a critical role in the body’s protection against both infection and injury. Preliminary research indicates that this is one reason why skin delivery of intradermal vaccinations and immunotherapies have repeatedly shown to be highly potent and effective.

 

Although mice humanized with skin grafts have been used in the past, this mouse model is technically challenging to achieve and is therefore not readily available for extensive preclinical testing, thereby rendering it highly ineffective for ongoing research. However, a recent study by Centlivre et al published in the journal Experimental Dermatology demonstrates that “the skin of HIS (human immune system) mice is colonized by human hematopoietic cells, mainly human T cells expressing CLA and exhibiting a memory phenotype.” By injecting this model with human antigen-presenting cells (APC) at the treatment site, Centlivre et al were able to invoke an immune response in the HIS mouse, thereby highlighting the potential these models have as an “innovative preclinical model for human skin immunity as well as for prospective analysis of vaccination via skin route, and notably DC therapies.”

 

Furthermore, the creation of a reliable murine model appropriate for in vivo research surrounding the interactions between vaccinations, immunotherapies and the human immune system should also afford biomedical scholars the opportunity to better understand “early events following immunotherapeutic administration,” making this particular strain of humanized mice that much more valuable in the lab setting.