Arming Immune Cells for Battle: A Brief Journey through the Advancements of T and NK Cell Immunotherapy

SIMPLE SUMMARY: This review is intended to provide an overview on the history and recent advances of T cell and natural killer (NK) cell-based immunotherapy. While the thymus was discovered as the origin of T cells in the 1960s, and NK cells were first described in 1975, the clinical application of adoptive cell therapies (ACT) only began in the early 1980s with the first lymphokine activated killer (LAK) cell product for the treatment of cancer patients. Over the past decades, further immunotherapies have been developed, including ACT using cytokine-induced killer (CIK) cells, products based on the NK cell line NK-92 as well as specific T and NK cell preparations. Recent advances have successfully improved the effectiveness of T, NK, CIK or NK-92 cells towards tumor-targeting antigens generated by genetic engineering of the immune cells. Herein, we summarize the promising development of ACT over the past decades in the fight against cancer. ABSTRACT: The promising development of adoptive immunotherapy over the last four decades has revealed numerous therapeutic approaches in which dedicated immune cells are modified and administered to eliminate malignant cells. Starting in the early 1980s, lymphokine activated killer (LAK) cells were the first ex vivo generated NK cell-enriched products utilized for adoptive immunotherapy. Over the past decades, various immunotherapies have been developed, including cytokine-induced killer (CIK) cells, as a peripheral blood mononuclear cells (PBMCs)-based therapeutic product, the adoptive transfer of specific T and NK cell products, and the NK cell line NK-92. In addition to allogeneic NK cells, NK-92 cell products represent a possible “off-the-shelf” therapeutic concept. Recent approaches have successfully enhanced the specificity and cytotoxicity of T, NK, CIK or NK-92 cells towards tumor-specific or associated target antigens generated by genetic engineering of the immune cells, e.g., to express a chimeric antigen receptor (CAR). Here, we will look into the history and recent developments of T and NK cell-based immunotherapy.