In a recent study titled “Activation and Propagation of Tumor-infiltrating Lymphocytes on Clinical-grade Designer Artificial Antigen-presenting Cells for Adoptive Immunotherapy of Melanoma” published in the Journal of Immunotherapy, a team of researchers has optimized a platform to expand tumor infiltrating lymphocytes (TILs) to a clinical scale using a genetically modified human leukemia cell line (K562).
The use of adoptive cell therapy with autologous TILs is already in clinical use to treat metastatic melanoma, with response rates of up to 50%. Nonetheless, generating enough TILs to transfer is a challenging process, and requires a pool of allogeneic normal donor peripheral blood mononuclear cells (PMBCs) used in vitro, to serve as the basis of a rapid expansion procedure.
In this study, researchers have managed to design an alternative option to PBMC feeders, by genetically modifying K562 cells to express several costimulatory molecules, such as CD86, CD137-ligand, and membrane-bound IL-15, allowing the team to use these cells as artificial antigen-presenting cells (aAPC), key players in an effective anti-tumoral T cell response.
The team used aAPCs as feeders to propagate TILs in vitro, and proceeded to measure the proliferation rates of these cells, alongside their activation and differentiation state.
The researchers found that aAPCs were as efficient feeders as PBMCs and increased the frequency of effector-memory CD8 T cells, which presented the same antitumor efficiency as those expanded with PBMCS. Furthermore these CD8 T cells showed an upregulation of genes in the Wnt and stem-cell pathways, when expanded with the aAPCs.
Overall, this study revealed that TILs, a group of cells present within the tumor microenvironment that are crucial in the fight against tumors, can be rapidly expanded with aAPC to a clinical scale, generating T cells with the same functions as those created using PMBCs. These results support a clinical application of aAPCs to create TILs for the treatment of melanoma.
