Rusckowski, M. | bioRxiv Science

bioRxiv2024

Oxygen Sensor-Guided Fine Needle Biopsy Studies of Human Cancer Xenografts in Mice

An oxygen sensor-mounted fine-needle biopsy tool was used for in vivo measurement of oxygen levels in tumor xenografts. The system provides a means of measuring the oxygen content in harvested tumor tissue from specific locations. Oxygen in human tumor xenografts in a murine model was observed for over 1 min. Tissues were mapped in relation to oxygen tension (pO2) readings and sampled for conventional cytological examination. Careful modeling of the pO2 readings over 60 seconds yielded a diffusion coefficient for oxygen at the sensor tip, providing additional diagnostic information about the tissue before sampling. Oxygen level measurement may provide a useful adjunct to the use of biomarkers in tumor diagnosis.

pathology↗

bioRxiv2022

Keratinocyte-tethering modification for biologics enables location-precise treatment in mouse vitiligo

Despite the central role of IFN{gamma} in vitiligo pathogenesis, systemic IFN{gamma} neutralization is an impractical treatment option due to strong immunosuppression. However, most vitiligo patients present with less than 20% affected body surface area, which provides an opportunity for localized treatments that avoid systemic side effects. After identifying keratinocytes as key cells that amplify IFN{gamma} signaling during vitiligo, we hypothesized that tethering an IFN{gamma} neutralizing antibody to keratinocytes would limit anti-IFN{gamma} effects to the treated skin for the localized treatment. To that end, we developed a bispecific antibody (BsAb) capable of blocking IFN{gamma} signaling while binding to desmoglein expressed by keratinocytes. We characterized the effect of the BsAb in vitro, ex vivo, and in a mouse model of vitiligo. SPECT/CT biodistribution and serum assays after local footpad injection revealed that the BsAb had improved skin retention, faster elimination from the blood, and less systemic IFN{gamma} inhibition than the non-tethered version. Furthermore, the BsAb conferred localized protection almost exclusively to the treated footpad during vitiligo that was not possible by local injection of the non-tethered anti-IFN{gamma} antibody. Thus, keratinocyte-tethering proved effective while significantly diminishing off-tissue effects of IFN{gamma} blockade, offering a new treatment strategy for localized skin diseases, including vitiligo.

immunology↗