Characterization of Liposomal Nanoparticles for in Vivo Conjugation to Adoptive Transferred T-Cells

Adoptive cell transfer (ACT) has proven to be a highly effective method for treating metastatic melanoma, however, the current procedure is expensive, requires expertise, and the adoptively transferred cells do not survive long in vivo. In order for the therapy to be effective multiple procedures would be required, further increasing the cost. This project aims to remove the need for repeated injections by arming adoptively transferred T-cells with liposomal nanoparticles. The nanoparticles are decorated with Interleukin-2 (IL-2) on the surface, which aids in targeting the nanoparticles to the adoptively transferred T-cells. Ideally, these nanoparticles will conjugate to the T-cells in vivo, since it has been shown that ex vivo conjugation has aided proliferation of T-cells and increased treatment efficacy.The nanoparticles will encapsulate a drug, SHP1/2 inhibitors, which will help prevent down-regulation of the immune response. The initial steps in this project include characterization of the nanoparticles, including determining the amount of IL-2 conjugated to the surface of the nanoparticles, the encapsulation efficiency, and the drug time release profile. From there, nanoparticles will be optimized to obtain more desirable encapsulation and drug release profiles.