Imaging Immune Cells Using Fc Domain Probes in Mouse Cancer Xenograft Models.

Wendy Bernhard,Kris Barreto,Ayman El-Sayed,C Ronald Geyer,John Decoteau

doi:10.3390/cancers14020300

Abstract

Simple SummaryThe immune system responds to abnormal cell growth by sending immune cells to kill them. The immune cell response is very important since it can usually stop abnormal cells from growing and spreading. Immuno-therapeutics used to treat cancer require help from the immune system to be effective. A biopsy is typically performed to determine the therapeutic efficacy of cancer treatment which is invasive and difficult. A simpler and less invasive way to monitor therapeutic efficacy is needed. Here, we show a molecule that can be used as an imaging agent to determine immune cell recruitment to tumors.Tracking immune responses is complex due to the mixture of cell types, variability in cell populations, and the dynamic environment. Tissue biopsies and blood analysis can identify infiltrating and circulating immune cells; however, due to the dynamic nature of the immune response, these are prone to sampling errors. Non-invasive targeted molecular imaging provides a method to monitor immune response, which has advantages of providing whole-body images, being non-invasive, and allowing longitudinal monitoring. Three non-specific Fc-containing proteins were labeled with near-infrared dye IRDye800CW and used as imaging probes to assess tumor-infiltrating immune cells in FaDu and A-431 xenograft models. We showed that Fc domains localize to tumors and are visible by fluorescent imaging. This tumor localization appears to be based on binding tumor-associated immune cells and some xenografts showed higher fluorescent signals than others. The Fc domain alone bound to different human immune cell types. The Fc domain can be a valuable research tool to study innate immune response.

Highlights

The innate immune system is the first to respond to infection or injury with recruitment of granulocytes and monocytes [1]
Four IgG1 Fc-containing imaging probes were expressed and purified in this study (Figure 1). These imaging probes consist of an IgG and a single-chain variable fragment fused to an Fc domain that bind maltose binding protein (MBP), a single heavy chain variable (VHH) fused to an Fc domain (VHH-Fc) that binds FaDu cells, and an Fc domain
We report for the first time the use of the hIgG Fc domain for imaging of immune cells in xenograft tumors in mice

Summary

Introduction

The innate immune system is the first to respond to infection or injury with recruitment of granulocytes and monocytes [1]. This sets off a cascade of signals amplifying the acute inflammatory response. Cancer cells use immune cells such as monocytes and neutrophils to aid in their development [3]. Having a way to identify the innate immune cell recruitment would be useful for disease diagnosis and treatment of cancer. Some therapies including doxorubicin, paclitaxel, and radiotherapy have been shown to increase monocyte recruitment and promote relapse, metastasis, and treatment resistance.

Methods

Results

Conclusion