Sodium iodide symporter (SLC5A5) (NIS)

The Sodium iodide symporter (NIS), also known as Solute carrier family 5 member 5 (SLC5A5), is a transmembrane glycoprotein that facilitates the active transport of iodide into cells using the electrochemical gradient of sodium (UniProt Q92911). In the context of Chimeric Antigen Receptor (CAR) T-cell therapy, NIS is utilized as a reporter gene to enable non-invasive, real-time monitoring of the engineered cells' biodistribution and expansion within the patient (Emami-Shahri et al., 2018, Sci Rep). By engineering CAR-T cells to co-express NIS, clinicians can utilize radiopharmaceuticals such as Iodine-124 for PET imaging or Technetium-99m pertechnetate for SPECT imaging to visualize the location of the T-cells (PubMed PMC5814439). This imaging capability is crucial for assessing whether CAR-T cells have successfully reached tumor sites and for identifying potential off-target accumulations. Furthermore, NIS can function as a theranostic tool; if the CAR-T cells cause severe toxicity, administration of high-dose Iodine-131 can be used to selectively ablate the NIS-expressing cells (Keu et al., 2017, Sci Transl Med). Safety considerations include the endogenous expression of NIS in the thyroid, salivary glands, and stomach, which can lead to background signal or off-target effects during imaging (StatPearls, Sodium Iodide Symporter).

Other names

Solute carrier family 5 member 5SLC5A5Na+/I- symporterSodium-iodide symporter

The sodium iodide symporter (NIS) mediates the active transport of one iodide ion (I-) against its concentration gradient, coupled with the symport of two sodium ions (Na+) down their electrochemical gradient, which is maintained by the Na+/K+ ATPase pump (UniProt Q92911).