Photochemical Treatment of Drosophila APCs Can Eliminate Associated Viruses and Maintain the APC Function for Generating Antigen-Specific CTLs Ex Vivo.

Jun Ye,Zeling Cai,Hong Yu,Chunxia Yang,Weixing Shi

doi:10.1155/2018/4167652

Abstract

Drosophila cells transfected with MHC class I and a number of costimulation molecules including B7.1, ICAM, LFA-3, and CD70 are potent antigen-presenting cells (APCs) for the generation of antigen-specific cytotoxic T cells (CTLs) in vitro. Using Drosophila APCs, CTLs specific for melanoma antigens have been generated in vitro and adoptively transferred to melanoma patients. However, the recent discovery that Drosophila cells can carry insect viruses raises the potential risk of Drosophila APCs transmitting xenogenic viruses to patient CTLs. In this study, we have investigated photoreactive methods to inactivate insect viruses in APC. A clinical grade psoralen compound, 8-MOP (UVADEX) in combination with UVA treatment (5 joules/cm2) can be used to inactivate Drosophila cell viruses. UVADEX treatment is sufficient to inactivate insect viruses but does not affect the expression of MHC class I molecules and costimulation molecules on Drosophila APCs. In fact, UVADEX treatment prevents Drosophila APC growth while maintaining APC function. Furthermore, UVADEX-treated Drosophila APCs maintain or have enhanced APC function as determined by enhanced T cell activation, proliferation, and CTL generation. Thus, the use of UVADEX-treated Drosophila APCs may provide a valuable tool for immunotherapy to generate tumor antigen-specific CTLs.

Highlights

Cancer immunotherapy, a type of treatment that pushes the immune system to attack tumors, has been ranked at the top of the list of scientific achievements in 2013 [1]
The recent discovery that Drosophila cells can carry insect viruses raises the potential risk of Drosophila antigen-presenting cells (APCs) transmitting viruses to patient cytotoxic T lymphocytes (CTLs) [8]
Previous studies have used Drosophila cells transfected with MHC class I molecule and costimulatory molecules as artificial APCs to generate antigen-specific

Summary

Introduction

A type of treatment that pushes the immune system to attack tumors, has been ranked at the top of the list of scientific achievements in 2013 [1]. Otherwise known as activated T cell therapy, has been developed to treat cancer [2, 3]. Adoptive cell immunotherapy involves activation of the patient’s own. CTLs are activated ex vivo by exposing naïve CD8+ T cells to antigenic peptide/MHC complexes presented by antigen-presenting cells (APCs). MHC complexes on APC leads to T cell proliferation and differentiation. Macrophages, and B cells can all function as APCs. In addition to MHC, the expression of several costimulatory molecules on APC is crucial for T cell activation. Once CD8+ T cells are activated, they are differentiated into armed CTLs. The armed CTLs are able to recognize and kill antigen-expressing target cells, such as virus-infected or cancer cells. Traditional antigen-presenting cells can be replaced by artificial antigen-presenting cells for the purpose of activating resting

Methods

Results

Conclusion